Citrus bacterial canker(CBC) is resulted from Xanthomonas citri subsp. citri(Xcc) infection and poses a significant threat to citrus production.Glutathione S-transferases(GSTs) are critical in maintaining redox homeos...Citrus bacterial canker(CBC) is resulted from Xanthomonas citri subsp. citri(Xcc) infection and poses a significant threat to citrus production.Glutathione S-transferases(GSTs) are critical in maintaining redox homeostasis in plants, especially in relation to abiotic and biotic stress responses. However, the function of GSTs in resisting CBC remains unclear. Here, citrus glutathione S-transferases were investigated applying a genome-wide approach. In total, 69 CsGSTs belonging to seven classes were identified, and the phylogeny, chromosomal distribution, gene structures and conserved motifs were analyzed. Several CsGSTs responded to Xcc infection, as observed in the upregulation of CsGSTF1 and CsGSTU18 in the CBC-sensitive ‘Wanjincheng' variety but not in the resistant ‘Kumquat' variety. CsGSTF1 and CsGSTU18 were localized at the cytoplasm. Transient overexpression of CsGSTF1 and CsGSTU18 mediated reactive oxygen species(ROS) scavenging, whereas the virus-induced gene silencing(VIGS) of CsGSTF1 and CsGSTU18 caused strong CBC resistance and ROS burst. The present study investigated the characterization of citrus GST gene family, and discovered that CsGSTF1 and CsGSTU18 negatively contributed to CBC through modulating ROS homeostasis. These findings emphasize the significance of GSTs in infection resistance in plants.展开更多
Specific activity, substrate specificity, and kinetic parameters （Km and Vmax） of glutathione S-transferases （GSTs） towards three substrates, 1-chloro-2,4-dinitrobenzene （CDNB）, 1,2-dichloro-4-nitrobenzene （DCN...Specific activity, substrate specificity, and kinetic parameters （Km and Vmax） of glutathione S-transferases （GSTs） towards three substrates, 1-chloro-2,4-dinitrobenzene （CDNB）, 1,2-dichloro-4-nitrobenzene （DCNB）, and p-nitrobenzene chloride （pNBC） were investigated in six tissues （foregut, midgut, hindgut, fat body, hemolymph, and muscle） of Oxya chinensis. In addition, the inhibition in vitro （ethacrynic acid, and Cibacron Blue 3GA） of Oxya chinensis in the six tissues was also investigated. Glutathione S-transferase activity was detected in all the six tissues examined. The rank order of GST activities towards CDNB was fat body 〉 midgut 〉 hindgut 〉 muscle 〉 foregut 〉 hemolymph both in females and males. Glutathione S-transferase activities in the fat body in females and males were 1.3- to 10.4-fold and 1.1- to 10.0- fold higher than those in the other tissues. The rank order of GST activities towards the other substrates changed slightly. From these results, it was inferred that GSTs in the fat body and midgut played important roles in detoxifying xenobiotics including insecticides and plant allelochemicals in O. chinensis. In the three substrates examined, CDNB seemed to be the best substrate, followed by pNBC and DCNB. The kinetic parameters of GSTs were different among the six tissues. This suggested that GSTs in different tissues have various affinities and catalytic efficiency to substrates. In vitro inhibition study showed that the median inhibition concentration （IC50） values of the two inhibitors to GSTs from the six tissues were different. The results suggested that the two inhibitors have different inhibition potency to GSTs from the different tissues. The observed changes in kinetic parameters and inhibition in vitro among the six tissues of the insect might suggest that the number and structure of isoenzymes and their rate of expression varied for the different tissues.展开更多
Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. We identified two glutathione S-transferase isoforms (V...Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. We identified two glutathione S-transferase isoforms (VpGSTS, sigma GST; VpGSTO, omega GST) from Venerupis philippinarum by RACE approaches. The open reading frames of VpGSTS and VpGSTO were of 612 bp and 729 bp, encoding 203 and 242 amino acids with an estimated molecular mass of 22.88 and 27.94 kDa, respectively. The expression profiles of VpGSTS and VpGSTO responded to heavy metals and benzo[a]pyrene (B[a]P) exposure were investigated by quantitative real-time RT-PCR. The expression of VpGSTS and VpGSTO were both rapidly up-regulated, however, they showed differential expression patterns to different toxicants. Cd displayed stronger induction of VpGSTS expression with an approximately 12-fold increase than that of VpGSTO with a maximum 6.4-fold rise. Cu exposure resulted in similar expression patterns for both VpGSTS and VpGSTO. For B[a]P exposure, the maximum induction of VpGSTO was approximately two times higher than that of VpGSTS. Altogether, these findings implied the involvement of VpGSTS and VpGSTO in host antioxidant responses, and highlighted their potential as a biomarker to Cd and B[a]P exposure.展开更多
Six antigenic peptides of Sm26/2 glutathione S-transferase of schistosoma mansoni have been predicted according to their hydrophilicity, flexibility, accessibility, charge distribution and beta-turn in the secondary s...Six antigenic peptides of Sm26/2 glutathione S-transferase of schistosoma mansoni have been predicted according to their hydrophilicity, flexibility, accessibility, charge distribution and beta-turn in the secondary structure by the determination of its primary structure, and synthesized by solid phase method. Two of them showed good antigenicity by Dot-ELISA. They would be candidate peptides of synthetic anti-schistosomal vaccine.展开更多
Glutathione S-transferases(GSTs)are a family of enzymes detoxifying various harmful compounds by conjugating them with glutathione.While primarily beneficial,dysregu-lation of GST activity or specific isoforms can con...Glutathione S-transferases(GSTs)are a family of enzymes detoxifying various harmful compounds by conjugating them with glutathione.While primarily beneficial,dysregu-lation of GST activity or specific isoforms can contribute to disease pathogenesis.The intricate balance of detoxification processes regulated by GSTs is pivotal in cellular homeostasis,whereby dysregulation in these mechanisms can have profound implications for human health.Certain GSTs neutralize carcinogens,shielding cells and potentially preventing tumorigenesis.Polymorphisms in specific GSTs may result in the accumulation of toxic metabolites,exacer-bating oxidative stress,inflammation,and DNA damage,notably observed in neurodegenera-tive diseases like Parkinson’s disease.They can also modulate signaling pathways involved in cell proliferation,survival,and apoptosis,with aberrant activity potentially contributing to un-controlled cell growth and resistance to cell death,thus promoting cancer development.They may also contribute to autoimmune diseases and chronic inflammatory conditions.This knowl-edge is useful for designing therapeutic interventions and understanding chemoresistance due to GST polymorphisms.A variety of GST inhibitors have been developed and investigated,with researchers actively working on new inhibitors aimed at preventing off-target effects.By leveraging knowledge of the involvement of specific GST isoforms in disease pathogenesis across different populations,more effective and targeted therapeutics can be designed to enhance patient care and improve treatment outcomes.展开更多
Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrat...Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrates in response to various stress conditions. Beyond their role in stress adaptation, certain GSTs are integral regulators of plant growth and development, contributing to a range of physiological processes. Most GST proteins exhibit dual enzymatic activities, functioning as both transferases and peroxidases, which enables their involvement in diverse cellular processes, including detoxification and stress responses. Recent advancements, particularly in X-ray crystallography, have enabled detailed structural analysis of GST proteins, significantly enhancing our understanding of their biological functions. This review offers a comprehensive overview of the classification and structural characteristics of GSTs in plants. It also highlights recent findings on their roles in plant growth and development, cell signaling, catalytic transport, and stress tolerance. Furthermore, key scientific challenges related to GSTs are discussed, focusing on their potential applications in agriculture. These insights aim to facilitate the screening of functional GST genes and support molecular breeding efforts across diverse crop species.展开更多
Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development...Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development.In this study,71 members of the BpGST family were identified from the entire Betula platyphylla Suk.genome.Most of the members encode proteins with amino acid lengths ranging from 101 to 875 and were localized to the cytoplasm by a prediction.BpGSTs can be divided into seven subfamilies,with a majority of birch U and F subfamily members according to gene structure,conserved motifs and evolutionary analysis.GST family genes showed collinearity with 22 genes in Oryza sativa L.,and three genes in Arabidopsis thaliana;promoter cis-acting elements predicted that the GST gene family is functional in growth,hormone regulation,and abiotic stress response.Most members of the F subfamily of GST(BpGSTFs)were expressed in roots,stems,leaves,and petioles,with the most expression observed in leaves.On the basis of the expression profiles of F subfamily genes(BpGSTF1 to BpGSTF13)during salt,mannitol and ABA stress,BpGSTF proteins seem to have multiple functions depending on the type of abiotic stress;for instance,BpGSTs may function at different times during abiotic stress.This study enhances understanding of the GST gene family and provides a basis for further exploration of their function in birch.展开更多
Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic con...Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic constants of glutathione S-transferases in M. troglodyta were studied. Significant differences in glutathione S-transferase activity and kinetic characteristics were observed among five instars of M. troglodyta larvae. Furthermore, the inhibition of glutathione S-transferase activity in five instars by 24 inhibitors was conducted. The results show the inhibition of GST activity of different instars by 24 inhibitors was different. For GST activity in the 1st instar, chlorpyrifos, lambda-cyhalothrin, endosulfan, abamectin, fipronil and pyridaben were the best inhibitors tested, and for GST activity in the 2nd instar, tannic acid and quercetin were the most potent inhibitors tested, and for GST activity in the 3rd instar, the inhibitory effects of quercetin, chlorpyrifos and lambda-cyhalothrin were the highest, and for GST activity in the 4th instar, quercetin and lambda-cyhalothrin were the best inhibitors, and the inhibitory effect of phoxim was the highest for GST activity in the 5th instar. Our results show that glutathione S-transferases in different instars are qualitatively different in isozyme composition and thus different in sensitivity to inhibitors.展开更多
Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
Objective： To evaluate the association of Glutathione S-transferase （GST） M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma （NPC） in a high risk area of Guangxi Zhuang Autonomous Regi...Objective： To evaluate the association of Glutathione S-transferase （GST） M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma （NPC） in a high risk area of Guangxi Zhuang Autonomous Region （province）, Southwest of China. Methods： A case-control study was conducted to investigate the genetic polymorphisms of these enzymes （GSTM1 and GSTT1 null genotypes）. A total of 127 NPC cases and 207 controls were recruited. Results： GSTM1 and GSTT1 null genotype frequencies were higher among NPC patients at a level of statistical significance （P〈0.005; P〈0.001 respectively）, and both GSTM1 and GSTT1 null genotype were even more significant （P〈0.001）. Conclusion： NPC is the most common cancer in Guangxi. GST enzymes are involved in the detoxification of many environmental carcinogens. Homozygous deletions of GSTM1 and GSTT1 have been associated with several types of cancer. The risk to develop NPC has been associated with environmental factors such as cigarette smoking and EB virus infection. The present results indicate that the GSTM1 and GSTT1 deletion polymorphisms are associated with an increase risk of susceptibility to NPC, and both detoxific enzyme genes deletion is more important than a single gene deletion for the susceptibility to NPC.展开更多
Objective Seminal vesiculitis is a prevalent infectious disease in the genitourinary system,but its intrinsic pathogenesis and molecular features remain unclear.Methods In this study,we utilized a next-generation sequ...Objective Seminal vesiculitis is a prevalent infectious disease in the genitourinary system,but its intrinsic pathogenesis and molecular features remain unclear.Methods In this study,we utilized a next-generation sequencing technology to demonstrate transcriptomic landscapes of clinical specimens from seminal vesiculitis patients.We identified enriched Go Ontology terms,pathway maps,processes,toxicity,and metabolic networks of seminal vesiculitis.Results Glutathione S-transferase activity is highly enriched,indicating its essential role in the disease's development.Furthermore,we established inflammation models of the seminal vesicle and verified the crucial function of glutathione S-transferase activity in these models.Conclusion Glutathione S-transferase serves an essential role in seminal vesiculitis patients.Our results shall provide a robust platform for further intensive studies of seminal vesiculitis.展开更多
AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcin...AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.展开更多
A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content （GSH） and glutathione S-transferase （GST, EC 2.5.1,18） activity in rice seedlings. The rice growth was severel...A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content （GSH） and glutathione S-transferase （GST, EC 2.5.1,18） activity in rice seedlings. The rice growth was severely inhibited when Cd level in the solution was higher than 10 mg/L. In rice shoots, GSH content and GST activity increased with the increasing Cd level, while in roots, GST was obviously inhibited by Cd treatments, Compared with shoots, the rice roots had higher GSH content and GST activity, indicating the ability of Cd detoxification was much higher in roots than in shoots. There was a significant correlation between Cd level and GSH content or GST activity, suggesting that both parameters may be used as biomarkers of Cd stress in rice.展开更多
Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidati...Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. Methods： Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction （PCR） and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species （ROS） generation, malondialdehyde （MDA）, protein carbonyls and glutathione （GSH） concentrations, and glutathione S-transferase （GST） activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. Results： Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for theGSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. Conclusion： Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.展开更多
AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study w...AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Pdymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.展开更多
Objective: The integrated method was investigated to measure Vm/Km of mouse liver glutathione S-transfer-ase (GST) activity on GSH and 7-Cl-4-nitrobenzofurazozan. Methods: Presetting concentration of one substrate twe...Objective: The integrated method was investigated to measure Vm/Km of mouse liver glutathione S-transfer-ase (GST) activity on GSH and 7-Cl-4-nitrobenzofurazozan. Methods: Presetting concentration of one substrate twenty-fold above the other's and taking maximum product absorbance Am as parameter while Km as constant, Vm/Km was obtained by nonlinear fitting of GST reaction curve to the integrated Michaelis-Menten equation In [Am/(Am -Ai)] + Ai/ ( ξ× Km ) = ( Vm/Km )×ti (1). Results: Vm/Km for GST showed slight dependence on initial substrate concentration and data range, but it was resistant to background absorbance, error in reaction origin and small deviation in presetting Km. Vm/Km was proportional to the amount of GST with upper limit higher than that by initial rate. There was close correlation between Vm/Km and initial rate of the same GST. Consistent results were obtained by this integrated method and classical initial rate method for the measurement of mouse liver GST. Conclusion: With the concentration of one substrate twenty-fold above the other's, this integrated method was reliable to measure the activity of enzyme on two substrates , and substrate concentration of the lower one close to its apparent Km was able to be used.展开更多
The reported effects of the glutathione S-transferase （GSTs） genes （GSTM1, GSTTI, and GSTP1） on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to inv...The reported effects of the glutathione S-transferase （GSTs） genes （GSTM1, GSTTI, and GSTP1） on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype （lle/Val ＋ Val/Val） with idiopathic infertility risk （odds ratio [OR]： 1.53; 95% confidence interval [CI]： 1.11-2.11; P = 0.009）. Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTTI-null and GSTP1 （lle/Val ＋ ValNal） （OR： 2.17; 95% Cl： 1.43-3.31; P = 0.0002）. These results suggest an increased risk of the GSTPI variant genotype （lle/Val ＋ Val/Val） for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 （especially the former） in modulating the risk of male infertility in males from Sichuan, southwest China.展开更多
AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking.METHODS: With consents, genotypes of the genes were determined using PCR methods for...AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking.METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking.RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64).These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR = 0.17 and 0.21 respectively.CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/fruit-related colorectal cancer risk, particularly in men of no smoking history.展开更多
Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-cont...Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）展开更多
Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of...Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(P.falciparum) isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods:A total of 70 P.falciparum isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year 2008-2009.The in vitro assessment of antimalarial activity of P.falciparum clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified assay.Results:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of P.falciparum isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was found.Based on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST gene.All isolates(70) also carried only one copy number of PfGST gene.There appears to be an association between amplification of PfGR gene and chloroquine resistance.The 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.展开更多
基金funded by the National Key Research and Development Program of China (Grant No.2022YFD1201600)Natural Science Foundation of Chongqing (Grant No.cstc2020jcyj-msxmX1064)+1 种基金Earmarked Funds for the China Agriculture Research System (Grant No.CARS-26)Three-year Action Plan of Xi'an University (Grant No.2021XDJH41)。
文摘Citrus bacterial canker(CBC) is resulted from Xanthomonas citri subsp. citri(Xcc) infection and poses a significant threat to citrus production.Glutathione S-transferases(GSTs) are critical in maintaining redox homeostasis in plants, especially in relation to abiotic and biotic stress responses. However, the function of GSTs in resisting CBC remains unclear. Here, citrus glutathione S-transferases were investigated applying a genome-wide approach. In total, 69 CsGSTs belonging to seven classes were identified, and the phylogeny, chromosomal distribution, gene structures and conserved motifs were analyzed. Several CsGSTs responded to Xcc infection, as observed in the upregulation of CsGSTF1 and CsGSTU18 in the CBC-sensitive ‘Wanjincheng' variety but not in the resistant ‘Kumquat' variety. CsGSTF1 and CsGSTU18 were localized at the cytoplasm. Transient overexpression of CsGSTF1 and CsGSTU18 mediated reactive oxygen species(ROS) scavenging, whereas the virus-induced gene silencing(VIGS) of CsGSTF1 and CsGSTU18 caused strong CBC resistance and ROS burst. The present study investigated the characterization of citrus GST gene family, and discovered that CsGSTF1 and CsGSTU18 negatively contributed to CBC through modulating ROS homeostasis. These findings emphasize the significance of GSTs in infection resistance in plants.
基金supported by the National Natural Science Foundation of China(30570247,30470219)Science and Technology Commission of Shanxi Province,China(041005,2006011075).
文摘Specific activity, substrate specificity, and kinetic parameters （Km and Vmax） of glutathione S-transferases （GSTs） towards three substrates, 1-chloro-2,4-dinitrobenzene （CDNB）, 1,2-dichloro-4-nitrobenzene （DCNB）, and p-nitrobenzene chloride （pNBC） were investigated in six tissues （foregut, midgut, hindgut, fat body, hemolymph, and muscle） of Oxya chinensis. In addition, the inhibition in vitro （ethacrynic acid, and Cibacron Blue 3GA） of Oxya chinensis in the six tissues was also investigated. Glutathione S-transferase activity was detected in all the six tissues examined. The rank order of GST activities towards CDNB was fat body 〉 midgut 〉 hindgut 〉 muscle 〉 foregut 〉 hemolymph both in females and males. Glutathione S-transferase activities in the fat body in females and males were 1.3- to 10.4-fold and 1.1- to 10.0- fold higher than those in the other tissues. The rank order of GST activities towards the other substrates changed slightly. From these results, it was inferred that GSTs in the fat body and midgut played important roles in detoxifying xenobiotics including insecticides and plant allelochemicals in O. chinensis. In the three substrates examined, CDNB seemed to be the best substrate, followed by pNBC and DCNB. The kinetic parameters of GSTs were different among the six tissues. This suggested that GSTs in different tissues have various affinities and catalytic efficiency to substrates. In vitro inhibition study showed that the median inhibition concentration （IC50） values of the two inhibitors to GSTs from the six tissues were different. The results suggested that the two inhibitors have different inhibition potency to GSTs from the different tissues. The observed changes in kinetic parameters and inhibition in vitro among the six tissues of the insect might suggest that the number and structure of isoenzymes and their rate of expression varied for the different tissues.
基金Supported by the 100 Talents Program of Chinese Academy of Sciences and Key Laboratory of Marine Spill Oil Identification and Damage Assessment Technology (No. 201115)the State Oceanic Administration of China
文摘Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. We identified two glutathione S-transferase isoforms (VpGSTS, sigma GST; VpGSTO, omega GST) from Venerupis philippinarum by RACE approaches. The open reading frames of VpGSTS and VpGSTO were of 612 bp and 729 bp, encoding 203 and 242 amino acids with an estimated molecular mass of 22.88 and 27.94 kDa, respectively. The expression profiles of VpGSTS and VpGSTO responded to heavy metals and benzo[a]pyrene (B[a]P) exposure were investigated by quantitative real-time RT-PCR. The expression of VpGSTS and VpGSTO were both rapidly up-regulated, however, they showed differential expression patterns to different toxicants. Cd displayed stronger induction of VpGSTS expression with an approximately 12-fold increase than that of VpGSTO with a maximum 6.4-fold rise. Cu exposure resulted in similar expression patterns for both VpGSTS and VpGSTO. For B[a]P exposure, the maximum induction of VpGSTO was approximately two times higher than that of VpGSTS. Altogether, these findings implied the involvement of VpGSTS and VpGSTO in host antioxidant responses, and highlighted their potential as a biomarker to Cd and B[a]P exposure.
文摘Six antigenic peptides of Sm26/2 glutathione S-transferase of schistosoma mansoni have been predicted according to their hydrophilicity, flexibility, accessibility, charge distribution and beta-turn in the secondary structure by the determination of its primary structure, and synthesized by solid phase method. Two of them showed good antigenicity by Dot-ELISA. They would be candidate peptides of synthetic anti-schistosomal vaccine.
基金would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2024-9/1).
文摘Glutathione S-transferases(GSTs)are a family of enzymes detoxifying various harmful compounds by conjugating them with glutathione.While primarily beneficial,dysregu-lation of GST activity or specific isoforms can contribute to disease pathogenesis.The intricate balance of detoxification processes regulated by GSTs is pivotal in cellular homeostasis,whereby dysregulation in these mechanisms can have profound implications for human health.Certain GSTs neutralize carcinogens,shielding cells and potentially preventing tumorigenesis.Polymorphisms in specific GSTs may result in the accumulation of toxic metabolites,exacer-bating oxidative stress,inflammation,and DNA damage,notably observed in neurodegenera-tive diseases like Parkinson’s disease.They can also modulate signaling pathways involved in cell proliferation,survival,and apoptosis,with aberrant activity potentially contributing to un-controlled cell growth and resistance to cell death,thus promoting cancer development.They may also contribute to autoimmune diseases and chronic inflammatory conditions.This knowl-edge is useful for designing therapeutic interventions and understanding chemoresistance due to GST polymorphisms.A variety of GST inhibitors have been developed and investigated,with researchers actively working on new inhibitors aimed at preventing off-target effects.By leveraging knowledge of the involvement of specific GST isoforms in disease pathogenesis across different populations,more effective and targeted therapeutics can be designed to enhance patient care and improve treatment outcomes.
基金funded by National Natural Science Foundation of China(grant no.32301870 to Chen Lin)Natural Science Foundation of Jiangsu Province(grant no.BK20230568 to Chen Lin)+3 种基金the Jiangsu Provincial Agricultural Science and Technology Independent Innovation Fund(grant no.CX(24)3124 to Chen Lin)Outstanding Ph.D.Programin Yangzhou(grant no.YZLYJFJH2022YXBS147 to Chen Lin)the General Project of Basic Scientific Research to colleges and universities in Jiangsu Province(grant no.22KJB210019 toChen Lin)the Priority Academic Program Development of Jiangsu Higher Education Institutions is greatly acknowledged.
文摘Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrates in response to various stress conditions. Beyond their role in stress adaptation, certain GSTs are integral regulators of plant growth and development, contributing to a range of physiological processes. Most GST proteins exhibit dual enzymatic activities, functioning as both transferases and peroxidases, which enables their involvement in diverse cellular processes, including detoxification and stress responses. Recent advancements, particularly in X-ray crystallography, have enabled detailed structural analysis of GST proteins, significantly enhancing our understanding of their biological functions. This review offers a comprehensive overview of the classification and structural characteristics of GSTs in plants. It also highlights recent findings on their roles in plant growth and development, cell signaling, catalytic transport, and stress tolerance. Furthermore, key scientific challenges related to GSTs are discussed, focusing on their potential applications in agriculture. These insights aim to facilitate the screening of functional GST genes and support molecular breeding efforts across diverse crop species.
基金supported by the National Key Research and Development Program of China(No.2021YFD2200304)FundamentalResearch Funds for the Central Universities(2572022DQ08)the National Natural Science Foundation of China(No32171738).
文摘Glutathione-S-transferase(GST,EC2.5.1.18)multifunctional protease is important for detoxification,defense against biotic and abiotic stresses,and secondary metabolic material transport for plant growth and development.In this study,71 members of the BpGST family were identified from the entire Betula platyphylla Suk.genome.Most of the members encode proteins with amino acid lengths ranging from 101 to 875 and were localized to the cytoplasm by a prediction.BpGSTs can be divided into seven subfamilies,with a majority of birch U and F subfamily members according to gene structure,conserved motifs and evolutionary analysis.GST family genes showed collinearity with 22 genes in Oryza sativa L.,and three genes in Arabidopsis thaliana;promoter cis-acting elements predicted that the GST gene family is functional in growth,hormone regulation,and abiotic stress response.Most members of the F subfamily of GST(BpGSTFs)were expressed in roots,stems,leaves,and petioles,with the most expression observed in leaves.On the basis of the expression profiles of F subfamily genes(BpGSTF1 to BpGSTF13)during salt,mannitol and ABA stress,BpGSTF proteins seem to have multiple functions depending on the type of abiotic stress;for instance,BpGSTs may function at different times during abiotic stress.This study enhances understanding of the GST gene family and provides a basis for further exploration of their function in birch.
基金supported by National Natural Science Foundation of China(Contract No.30600476 and 30972376)
文摘Micromelalopha troglodyta （Graeser） is an important pest of poplar in China. Glutathione S-transferases （GSTs） are known to be responsible for adaptation mechanisms of M. troglodyta. The activities and kinetic constants of glutathione S-transferases in M. troglodyta were studied. Significant differences in glutathione S-transferase activity and kinetic characteristics were observed among five instars of M. troglodyta larvae. Furthermore, the inhibition of glutathione S-transferase activity in five instars by 24 inhibitors was conducted. The results show the inhibition of GST activity of different instars by 24 inhibitors was different. For GST activity in the 1st instar, chlorpyrifos, lambda-cyhalothrin, endosulfan, abamectin, fipronil and pyridaben were the best inhibitors tested, and for GST activity in the 2nd instar, tannic acid and quercetin were the most potent inhibitors tested, and for GST activity in the 3rd instar, the inhibitory effects of quercetin, chlorpyrifos and lambda-cyhalothrin were the highest, and for GST activity in the 4th instar, quercetin and lambda-cyhalothrin were the best inhibitors, and the inhibitory effect of phoxim was the highest for GST activity in the 5th instar. Our results show that glutathione S-transferases in different instars are qualitatively different in isozyme composition and thus different in sensitivity to inhibitors.
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
文摘Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
文摘Objective： To evaluate the association of Glutathione S-transferase （GST） M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma （NPC） in a high risk area of Guangxi Zhuang Autonomous Region （province）, Southwest of China. Methods： A case-control study was conducted to investigate the genetic polymorphisms of these enzymes （GSTM1 and GSTT1 null genotypes）. A total of 127 NPC cases and 207 controls were recruited. Results： GSTM1 and GSTT1 null genotype frequencies were higher among NPC patients at a level of statistical significance （P〈0.005; P〈0.001 respectively）, and both GSTM1 and GSTT1 null genotype were even more significant （P〈0.001）. Conclusion： NPC is the most common cancer in Guangxi. GST enzymes are involved in the detoxification of many environmental carcinogens. Homozygous deletions of GSTM1 and GSTT1 have been associated with several types of cancer. The risk to develop NPC has been associated with environmental factors such as cigarette smoking and EB virus infection. The present results indicate that the GSTM1 and GSTT1 deletion polymorphisms are associated with an increase risk of susceptibility to NPC, and both detoxific enzyme genes deletion is more important than a single gene deletion for the susceptibility to NPC.
基金supported by the Six Talent Peak Project of High-level Talents in Jiangsu Province (No. WSW-017 to Liu B)Medical research key project of Jiangsu Provincial Health Commission (No. K2023030 to Liu B)+1 种基金National Natural Science Foundation of China (No. 82203115 to Miao C), Natural Science Foundation of Jiangsu Province (No. BK20220726 to Miao C)Jiangsu Province Capability Improvement Project through Science, Technology and Education (No. ZDXK202219 to Wang Z).
文摘Objective Seminal vesiculitis is a prevalent infectious disease in the genitourinary system,but its intrinsic pathogenesis and molecular features remain unclear.Methods In this study,we utilized a next-generation sequencing technology to demonstrate transcriptomic landscapes of clinical specimens from seminal vesiculitis patients.We identified enriched Go Ontology terms,pathway maps,processes,toxicity,and metabolic networks of seminal vesiculitis.Results Glutathione S-transferase activity is highly enriched,indicating its essential role in the disease's development.Furthermore,we established inflammation models of the seminal vesicle and verified the crucial function of glutathione S-transferase activity in these models.Conclusion Glutathione S-transferase serves an essential role in seminal vesiculitis patients.Our results shall provide a robust platform for further intensive studies of seminal vesiculitis.
文摘AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.
基金This work was financially supported by the National Natural Science Foundation of China(Grant No.30700479)China Postdoctoral Science Foundation(Grant No.20060390288).
文摘A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content （GSH） and glutathione S-transferase （GST, EC 2.5.1,18） activity in rice seedlings. The rice growth was severely inhibited when Cd level in the solution was higher than 10 mg/L. In rice shoots, GSH content and GST activity increased with the increasing Cd level, while in roots, GST was obviously inhibited by Cd treatments, Compared with shoots, the rice roots had higher GSH content and GST activity, indicating the ability of Cd detoxification was much higher in roots than in shoots. There was a significant correlation between Cd level and GSH content or GST activity, suggesting that both parameters may be used as biomarkers of Cd stress in rice.
文摘Aim： To examine whether a relationship exists between glutathione S-transferase Mu-1 （GSTM1） gene polymorphism and the susceptibility of sperm and seminal plasma from patients with idiopathic infertility to oxidative stress. Methods： Fifty-two men with idiopathic infertility and 60 healthy fertile men were recruited to this study. GSTM1 gene polymorphism was determined by polymerase chain reaction （PCR） and both the infertile and control individuals were divided into GSTM1 null and GSTM1 positive groups according to their GSTM1 gene structure. We compared reactive oxygen species （ROS） generation, malondialdehyde （MDA）, protein carbonyls and glutathione （GSH） concentrations, and glutathione S-transferase （GST） activity in seminal plasma and spermatozoa from infertile patients and controls with respect to GSTM1 genotype. Results： Significantly higher levels of oxidative stress and damage markers were found in idiopathic infertile men with the GSTM1 null genotype compared with those with the GSTM1 positive genotype. There was no significant difference in genotype distribution for theGSTM1 variant between the idiopathic infertile subjects and fertile subjects. Patients with the GSTM1 null genotype also had lower sperm concentrations than those with GSTM1 positive genotype. Conclusion： Our results suggest that the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype compared with those possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1 polymorphism might be an important source of variation in susceptibility of spermatozoa to oxidative damage.
基金Supported by The Natural Scientific Foundation of China No. 39860032by the Education Department of Guangxi Zhuang Autonomous Region No. 98-2-8
文摘AIM: Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism of a wide range of carcinogens, but deletions of the genes are commonly found in the population. The present study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: The genetic polymorphisms were studied at an aflatoxin highly contaminated region in Guangxi, China. Pdymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in blood samples. The case group was composed of 181 patients of HCC identified by the pathologists and the control group was composed of 360 adults without any tumor. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in the control were 47.8% and 42.7%, while those in the HCC group were 64.6% and 59.7%, respectively. The differences between HCC group and control group were very significant (P<0.01). GSTM1 and GSTT1 combined null genotypes in HCC group and control group were 38.2% and 18.5% respectively, and the difference was significant (P<0.05). CONCLUSION: The GSTM1 and GSTT1 null genotypes are associated with an increased risk of HCC in a special geographic environment. Combination of the two null genotypes in an individual is substantially increased twice the risk of HCC.
基金National Natural Science Foundation of China (No.30200266)
文摘Objective: The integrated method was investigated to measure Vm/Km of mouse liver glutathione S-transfer-ase (GST) activity on GSH and 7-Cl-4-nitrobenzofurazozan. Methods: Presetting concentration of one substrate twenty-fold above the other's and taking maximum product absorbance Am as parameter while Km as constant, Vm/Km was obtained by nonlinear fitting of GST reaction curve to the integrated Michaelis-Menten equation In [Am/(Am -Ai)] + Ai/ ( ξ× Km ) = ( Vm/Km )×ti (1). Results: Vm/Km for GST showed slight dependence on initial substrate concentration and data range, but it was resistant to background absorbance, error in reaction origin and small deviation in presetting Km. Vm/Km was proportional to the amount of GST with upper limit higher than that by initial rate. There was close correlation between Vm/Km and initial rate of the same GST. Consistent results were obtained by this integrated method and classical initial rate method for the measurement of mouse liver GST. Conclusion: With the concentration of one substrate twenty-fold above the other's, this integrated method was reliable to measure the activity of enzyme on two substrates , and substrate concentration of the lower one close to its apparent Km was able to be used.
文摘The reported effects of the glutathione S-transferase （GSTs） genes （GSTM1, GSTTI, and GSTP1） on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype （lle/Val ＋ Val/Val） with idiopathic infertility risk （odds ratio [OR]： 1.53; 95% confidence interval [CI]： 1.11-2.11; P = 0.009）. Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTTI-null and GSTP1 （lle/Val ＋ ValNal） （OR： 2.17; 95% Cl： 1.43-3.31; P = 0.0002）. These results suggest an increased risk of the GSTPI variant genotype （lle/Val ＋ Val/Val） for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 （especially the former） in modulating the risk of male infertility in males from Sichuan, southwest China.
基金Supported by National Science Council No. 89-2314-B-002-373,90-2320-B-002-123 and 91-2320-B-002-121National Health Research Institute No. 85-HR-516, 86-HR-516, and 87-HR-516
文摘AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking.METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking.RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64).These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR = 0.17 and 0.21 respectively.CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/fruit-related colorectal cancer risk, particularly in men of no smoking history.
文摘Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）
基金supported by Thammasat University and The Commission on Higher Education,Ministry of Education of Thailand
文摘Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(P.falciparum) isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods:A total of 70 P.falciparum isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year 2008-2009.The in vitro assessment of antimalarial activity of P.falciparum clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified assay.Results:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of P.falciparum isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was found.Based on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST gene.All isolates(70) also carried only one copy number of PfGST gene.There appears to be an association between amplification of PfGR gene and chloroquine resistance.The 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.
