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
This case-control study evaluated the frequency of Glutathione S-transferase Mu 1(GSTM1)deletion and Glutathione S-transferase Alpha 1(GSTA1)mutation in chronic obstructive pulmonary disease(COPD)patients,whether they...This case-control study evaluated the frequency of Glutathione S-transferase Mu 1(GSTM1)deletion and Glutathione S-transferase Alpha 1(GSTA1)mutation in chronic obstructive pulmonary disease(COPD)patients,whether they had concomitant lung squamous cell carcinoma(LSCC)or not,to assess their connection with cancer susceptibility.By means of multivariate logistic regression analysis,the GSTM1 null genotype serves as a significant standalone risk factor for LSCC,in addition to variables like age,smoking history,emphysema,body mass index(BMI),albumin level,and neutrophil-to-lymphocyte ratio(NLR).A predictive model incorporating these factors demonstrated superior discriminative ability compared to the established COPD Lung Cancer Screening Score(COPD-LUCSS).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
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
AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South...AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population. METHODS: We conducted a population-based, large- scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSI-F1 were determined using realtime PCR. RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer. CONCLUSION: GSTM1 and GSCI-1 null genotypes were not associated with increased risk of GC or CRC in Koreans.展开更多
AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients.Among them,18 pa...AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients.Among them,18 patients were mismatched for the glutathione S-transferase T1(GSTT1)alleles(don+/rec-),and 4 were matched(don+/rec+).Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection(former de novo immune hepatitis).For the detection of specific Tlymphocytes,peripheral blood mononuclear cells were collected and stored in liquid nitrogen.The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made,15-mer overlapping peptides,which covered the entire GSTT1 amino acid sequence.The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8,CD4,IL-4 and IFNγ.RESULTS Activation of CD8^+T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection(3 out of 7),with production of IL-4 and/or IFNγat a rate of 1%-4.92%depending on the peptides.The CD4^+response was most common and not exclusive for patients with the disease,where 5 out of 7 showed percentages of activated cells from 1.24%to 31.34%.Additionally,two patients without the disease but with the mismatch had cells that became stimulated with some peptides(1.45%-5.18%).Highly unexpected was the finding of a double positive CD4^+CD8^(low)T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch,in 4 patients with plasma cell-rich rejection and in 3 patients without the disease.Unfortunately,CD4^+CD8^(low)cells represent 1%of the total number of lymphocytes,and stimulation could not be analyzed in 9 patients due to the low number of gated cells.Cells from the 4 patients included as controls did not show activation with any of the peptides.CONCLUSION Patients with GSTT1 mismatch can develop a specific T-cell response,but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown.展开更多
Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, ...Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.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
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 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
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
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
IM To detect glutathione Stransferase placental (GSTP) mRNA expression in hepatic preneoplastic lesions in rats.METHODS Using SolitFarber model, the GSTP mRNA expression was observed in hepatic preneoplastic lesio...IM To detect glutathione Stransferase placental (GSTP) mRNA expression in hepatic preneoplastic lesions in rats.METHODS Using SolitFarber model, the GSTP mRNA expression was observed in hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) in rats and normal and regenerated hepatic tissues in the control group by in situ hybridization.RESULTS GSTP mRNA was mainly expressed in altered hepatic foci (AHF) and some of the oval cells in hepatic preneoplastic lesions and the extent of its expression was different among various foci or/and positive cells in the same focus whereas no expression was observed in normal and regenerated hepatic tissues.CONCLUSION Cells in AHF and oval cells may be the preneoplastic cells in the experimental hepatocellular carcinoma at the molecular level and heterogeneity exists in GSTP transcription levels..展开更多
Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorph...Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. Methods PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. Results The polymorphisms at locus of GSTP1- A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n =118) bore only homogenous wild genotype (C2293/ C2293) at GSTP1 - C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P=0.09, OR=1.96, 95% CI 0.89-4.32,). Conclusion This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.展开更多
The response of glutathione(GSH) content and glutathione S-transferease(GST) activity to the acetochlor in roots and shoots of the maize 'Dongnong248',the sorghum 'Aoza No.2' and millet'Yugu' w...The response of glutathione(GSH) content and glutathione S-transferease(GST) activity to the acetochlor in roots and shoots of the maize 'Dongnong248',the sorghum 'Aoza No.2' and millet'Yugu' was evaluated.The concentrations of pre-emergence acetochlor causing a 50% inhibition of plant shoot height were 25 μmol·L^(-1) for the tolerant 'Dongnong248' maize,5 μmol·L^(-1) for the sensitive 'Aoza No.2' sorghum and 0.5 μmol·L^(-1) for the very sensitive 'Yugu'millet.Pre-treatment with 10 μmol·L^(-1) of acetochlor induced the root GST activities and nonprotein thiol content of all three cultivars.The induction of root GST activities and nonprotein thiol content compared to controls are observed on the fourth day after acetochlor treatment,The extents of activity and content increase from the higher to the lower were:tolerant maize cultivar 'Dongnong248'>sorghum cultivar'Aoza No.2'>millet cultivar 'Yugu'.The activities and contents induced in shoots were similar to that in roots,but the degrees of increase were less.Under different concentration treatment,the thiol content and GST activities increased with the herbicide concentration rising,then reached their peaks and began to decrease in all tested crop seedlings.The extent of induced GST activities and thiol content correlated well with differential cultivar resistance to acetochlor,so their protective mechanism appears to be strongly dependent on the endogenous levels of GSH and activities of GST.展开更多
Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histoco...Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis(dn AIH) when studied. In its latest update, the Banff Working Group for liver allograft pathology proposed replacing the term dn AIH with plasma cell(PC)-rich rejection. Antibodies to glutathione S-transferase T1(GSTT1) in null recipients of GSTT1 positive donors have been included as a contributory but nonessential feature of the diagnosis of PC-rich rejection. Also in this update, non-organ-specific anti-nuclear or smooth muscle autoantibodies are no longer included as diagnostic criteria. Although initially found in a proportion of patients with PC-rich rejection, the presence of autoantibodies is misleading since they are not diseasespecific and appear in many different contexts as bystanders. The cellular types and proportions of the inflammatory infiltrates in diagnostic biopsies have been studied in detail very recently. PC-rich rejection biopsies present a characteristic cellular profile with a predominance of T lymphocytes and a high proportion of PCs, close to 30%, of which 16.48% are Ig G4+. New data on the relevance of GSTT1-specific T lymphocytes to PC-rich rejection will be discussed in this review.展开更多
Glutathione S-transferases (GSTs) are phase II enzymes that facilitate the detoxification of xenobioties and play important roles in antioxidant defense. We investigated the expression patterns of seven Venerupis ph...Glutathione S-transferases (GSTs) are phase II enzymes that facilitate the detoxification of xenobioties and play important roles in antioxidant defense. We investigated the expression patterns of seven Venerupis philippinarum GSTs (VpGSTs) and four Mytilus galloprovincialis GSTs (MgGSTs) following exposure to BDE-47. Differential expressions of the seven VpGSTs and four MgGSTs transcripts were observed, with differences between the hepatopancreas and gills. Among these GSTs, the sigma classes (VpGSTS1, VpGSTS2, VpGSTS3, MgGST1, and MgGST3) were highly expressed in response to BDE-47 exposure, demonstrating their potential as molecular biomarkers for environmental biomonitoring studies. We obtained the three-dimensional crystal structures of VpGSTs and MgGSTs by homologous modeling. A model to elucidate the binding interactions between the ligands and receptors was defined by molecular docking, Hydrophobic and n were the most often observed interactions between BDE-47 and the GSTs.展开更多
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Anhui Province’s Clinical Medical Research Transformation Special Initiative(Project No.:202204295107020016)。
文摘This case-control study evaluated the frequency of Glutathione S-transferase Mu 1(GSTM1)deletion and Glutathione S-transferase Alpha 1(GSTA1)mutation in chronic obstructive pulmonary disease(COPD)patients,whether they had concomitant lung squamous cell carcinoma(LSCC)or not,to assess their connection with cancer susceptibility.By means of multivariate logistic regression analysis,the GSTM1 null genotype serves as a significant standalone risk factor for LSCC,in addition to variables like age,smoking history,emphysema,body mass index(BMI),albumin level,and neutrophil-to-lymphocyte ratio(NLR).A predictive model incorporating these factors demonstrated superior discriminative ability compared to the established COPD Lung Cancer Screening Score(COPD-LUCSS).
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 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.
文摘AIM: To evaluate the association of glutathione S-trans-ferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population. METHODS: We conducted a population-based, large- scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSI-F1 were determined using realtime PCR. RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer. CONCLUSION: GSTM1 and GSCI-1 null genotypes were not associated with increased risk of GC or CRC in Koreans.
基金Supported by The Spanish Ministry of Economy,Instituto de Salud Carlos III,Nos.10/2332 and 11/857the Andalusian government,No.PI-0332-2007,for which Martinez-Bravo MJ was a pre-doctoral fellow
文摘AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts.METHODS The study group included 22 liver transplant patients.Among them,18 patients were mismatched for the glutathione S-transferase T1(GSTT1)alleles(don+/rec-),and 4 were matched(don+/rec+).Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection(former de novo immune hepatitis).For the detection of specific Tlymphocytes,peripheral blood mononuclear cells were collected and stored in liquid nitrogen.The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made,15-mer overlapping peptides,which covered the entire GSTT1 amino acid sequence.The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8,CD4,IL-4 and IFNγ.RESULTS Activation of CD8^+T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection(3 out of 7),with production of IL-4 and/or IFNγat a rate of 1%-4.92%depending on the peptides.The CD4^+response was most common and not exclusive for patients with the disease,where 5 out of 7 showed percentages of activated cells from 1.24%to 31.34%.Additionally,two patients without the disease but with the mismatch had cells that became stimulated with some peptides(1.45%-5.18%).Highly unexpected was the finding of a double positive CD4^+CD8^(low)T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch,in 4 patients with plasma cell-rich rejection and in 3 patients without the disease.Unfortunately,CD4^+CD8^(low)cells represent 1%of the total number of lymphocytes,and stimulation could not be analyzed in 9 patients due to the low number of gated cells.Cells from the 4 patients included as controls did not show activation with any of the peptides.CONCLUSION Patients with GSTT1 mismatch can develop a specific T-cell response,but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown.
文摘Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.
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.
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 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.
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.
文摘IM To detect glutathione Stransferase placental (GSTP) mRNA expression in hepatic preneoplastic lesions in rats.METHODS Using SolitFarber model, the GSTP mRNA expression was observed in hepatic preneoplastic lesions induced by diethylnitrosamine (DEN) in rats and normal and regenerated hepatic tissues in the control group by in situ hybridization.RESULTS GSTP mRNA was mainly expressed in altered hepatic foci (AHF) and some of the oval cells in hepatic preneoplastic lesions and the extent of its expression was different among various foci or/and positive cells in the same focus whereas no expression was observed in normal and regenerated hepatic tissues.CONCLUSION Cells in AHF and oval cells may be the preneoplastic cells in the experimental hepatocellular carcinoma at the molecular level and heterogeneity exists in GSTP transcription levels..
文摘Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. Methods PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. Results The polymorphisms at locus of GSTP1- A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n =118) bore only homogenous wild genotype (C2293/ C2293) at GSTP1 - C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P=0.09, OR=1.96, 95% CI 0.89-4.32,). Conclusion This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.
文摘The response of glutathione(GSH) content and glutathione S-transferease(GST) activity to the acetochlor in roots and shoots of the maize 'Dongnong248',the sorghum 'Aoza No.2' and millet'Yugu' was evaluated.The concentrations of pre-emergence acetochlor causing a 50% inhibition of plant shoot height were 25 μmol·L^(-1) for the tolerant 'Dongnong248' maize,5 μmol·L^(-1) for the sensitive 'Aoza No.2' sorghum and 0.5 μmol·L^(-1) for the very sensitive 'Yugu'millet.Pre-treatment with 10 μmol·L^(-1) of acetochlor induced the root GST activities and nonprotein thiol content of all three cultivars.The induction of root GST activities and nonprotein thiol content compared to controls are observed on the fourth day after acetochlor treatment,The extents of activity and content increase from the higher to the lower were:tolerant maize cultivar 'Dongnong248'>sorghum cultivar'Aoza No.2'>millet cultivar 'Yugu'.The activities and contents induced in shoots were similar to that in roots,but the degrees of increase were less.Under different concentration treatment,the thiol content and GST activities increased with the herbicide concentration rising,then reached their peaks and began to decrease in all tested crop seedlings.The extent of induced GST activities and thiol content correlated well with differential cultivar resistance to acetochlor,so their protective mechanism appears to be strongly dependent on the endogenous levels of GSH and activities of GST.
基金Supported by Andalusian government,Proyecto de Excelencia,No.CTS-7846Spanish Ministry of Economy,Instituto de Salud Carlos Ⅲ,No.11/857 and No.17/1403
文摘Antibody-mediated rejection(AMR) in liver transplantation has long been underestimated. The concept of the liver as an organ susceptible to AMR has emerged in recent years, not only in the context of the major histocompatibility complex with the presence of HLA donor-specific antibodies, but also with antigens regarded as "minor", whose role in AMR has been demonstrated. Among them, antibodies against glutathione S-transferase T1 have been found in 100% of patients with de novo autoimmune hepatitis(dn AIH) when studied. In its latest update, the Banff Working Group for liver allograft pathology proposed replacing the term dn AIH with plasma cell(PC)-rich rejection. Antibodies to glutathione S-transferase T1(GSTT1) in null recipients of GSTT1 positive donors have been included as a contributory but nonessential feature of the diagnosis of PC-rich rejection. Also in this update, non-organ-specific anti-nuclear or smooth muscle autoantibodies are no longer included as diagnostic criteria. Although initially found in a proportion of patients with PC-rich rejection, the presence of autoantibodies is misleading since they are not diseasespecific and appear in many different contexts as bystanders. The cellular types and proportions of the inflammatory infiltrates in diagnostic biopsies have been studied in detail very recently. PC-rich rejection biopsies present a characteristic cellular profile with a predominance of T lymphocytes and a high proportion of PCs, close to 30%, of which 16.48% are Ig G4+. New data on the relevance of GSTT1-specific T lymphocytes to PC-rich rejection will be discussed in this review.
基金Supported by the National Natural Science Foundation of China(No.21107136)the International Foundation for Science(No.F/5230-1)
文摘Glutathione S-transferases (GSTs) are phase II enzymes that facilitate the detoxification of xenobioties and play important roles in antioxidant defense. We investigated the expression patterns of seven Venerupis philippinarum GSTs (VpGSTs) and four Mytilus galloprovincialis GSTs (MgGSTs) following exposure to BDE-47. Differential expressions of the seven VpGSTs and four MgGSTs transcripts were observed, with differences between the hepatopancreas and gills. Among these GSTs, the sigma classes (VpGSTS1, VpGSTS2, VpGSTS3, MgGST1, and MgGST3) were highly expressed in response to BDE-47 exposure, demonstrating their potential as molecular biomarkers for environmental biomonitoring studies. We obtained the three-dimensional crystal structures of VpGSTs and MgGSTs by homologous modeling. A model to elucidate the binding interactions between the ligands and receptors was defined by molecular docking, Hydrophobic and n were the most often observed interactions between BDE-47 and the GSTs.