Objective:To systematically review the effects of administering metformin and glutathione alone and in coformulation with other compounds on the fertility and reproductive health of diabetic male rodents.Methods:The g...Objective:To systematically review the effects of administering metformin and glutathione alone and in coformulation with other compounds on the fertility and reproductive health of diabetic male rodents.Methods:The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA)were followed to conduct this systematic review.Studies published until August 2024 in PubMed,Web of Science,and Scopus databases were searched,identified,screened,and selected for a detailed review.The keywords included metformin,diabetes,reproduction,glutathione,and rodent models.Results:A total of 166 studies were identified,of which 11 met the inclusion criteria and were included in the qualitative synthesis.One additional study was identified through snowballing and citation tracking,bringing the total to 12 studies.The findings indicate that metformin and glutathione,administered alone or in combination with other compounds,improved sperm count,motility,and morphology;restored reproductive hormone levels;reduced oxidative stress markers;and improved testicular histopathology in diabetic male rodents.Conclusions:Coformulation of metformin and glutathione with other compounds was found to be more effective in improving fertility and reproductive parameters in diabetic male rodents compared to mono-administration.However,further studies on the coformulation of metformin and glutathione are needed to confirm their efficacy and elucidate the underlying mechanisms.Study registration:The study protocol was registered in the International Prospective Register of Systematic Reviews(PROSPERO)with registration number CRD42024561820.展开更多
Background Environmental hypoxia is a common phenomenon in aquaculture,which causes gill tissue injury in fish.Glutathione(GSH)is a vital antioxidant in animal tissues,and its levels decrease under hypoxic conditions....Background Environmental hypoxia is a common phenomenon in aquaculture,which causes gill tissue injury in fish.Glutathione(GSH)is a vital antioxidant in animal tissues,and its levels decrease under hypoxic conditions.However,the effects of glutathione on fish under hypoxic stress remain poorly understood.This study aimed to investigate the impact of glutathione on gill tissue damage in fish under hypoxic stress and explore the underlying mechanisms.Methods Six experimental diets with varying glutathione concentrations.The actual glutathione levels in these diets,measured by high-performance liquid chromatography,were 0.00,145.95,291.90,437.85,583.80,and 729.75 mg/kg,respectively.Fish were fed these diets for 70 d,after which a 96-h hypoxic stress experiment was conducted.The experiment was set up with normoxic and hypoxic groups,in which the dissolved oxygen in the group was 6 mg/L,and that in the group was 1 mg/L.Results This research revealed that glutathione could enhance the growth performance and antioxidant capability of juvenile grass carp while mitigating the structural damage to gill tissues induced by hypoxia stress.Mechanistic investigations further indicated that glutathione mitigated hypoxia-induced oxidative injury in gill tissues and improved their antioxidant capacity.In addition,glutathione attenuated gill apoptosis induced by hypoxia stress.Glutathione also inhibited the initiation,nucleation,elongation,and degradation phases of autophagy,thereby attenuating hypoxia-induced gill autophagy.Moreover,glutathione was found to alleviate hypoxia-induced endoplasmic reticulum stress(ERS)in gills,a response potentially linked to the suppression of PERK,IRE1,and ATF6 signaling pathways.Finally,based on the ROS and PC contents in gill tissue,the optimum glutathione supplementation levels for juvenile grass carp under hypoxia stress were 437.10 and 495.00 mg/kg,respectively.Conclusions In conclusion,our experimental results demonstrated the effectiveness of glutathione in alleviating gill tissue damage caused by hypoxic stress.This study confirms the feasibility and effectiveness of dietary glutathione addition to alleviate hypoxic stress in fish.展开更多
Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highli...Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highlights the selective vulnerability of neurons to the insults of reactive oxygen species.The motor symptoms of PD are caused by degeneration of dopamine neurons in the substantia nigra.These neurons experience increased oxidative stress due in part to highly active mitochondria that support their high bioenergetic demand and the generation of reactive oxygen species by dopamine metabolism(Watanabe et al.,2024).展开更多
Smart pesticide delivery systems based on stimuli-responsive nanocarriers have attracted considerable attention because of their potential to enhance pesticide efficiency while reducing environmental risks.In this stu...Smart pesticide delivery systems based on stimuli-responsive nanocarriers have attracted considerable attention because of their potential to enhance pesticide efficiency while reducing environmental risks.In this study,a novel p H/glutathione dual-responsive pesticide delivery system was constructed through the synthesis of disulfide-bridged hollow mesoporous organosilica nanospheres(HMONs)via the St??ber method,followed by poly(acrylic acid)(PAA)coating through distillation-precipitation polymerization to form HMONs@PAA nanocomposites.The resulting abamectin-loaded system(Abamectin-HMONs@PAA)demonstrated a 12.73% pesticide loading capacity and significantly improved photostability,retaining twice as much active ingredient as free abamectin after 250 h of UV irradiation(36 W).Release studies revealed p H-and glutathione-dependent characteristics,with cumulative releases in acidic conditions exceeding those in neutral and alkaline environments by 18.66% and 40.98%,respectively,and a 14.2% increase in glutathione-containing solution(0.2 mmol·L^(-1) in 70% ethanol)after 97 h.Bioassays showed superior performance against Plutella xylostella,with a 13.33% reduction in survival rate compared to conventional suspension at equivalent dosage(40 mg·L^(-1)),while maintaining efficacy after extensive rainfall simulation(20 events over 10 days).This study provides a promising approach for developing environmentally responsive nanopesticides with enhanced durability and controlled-release properties,offering significant potential for sustainable crop protection.展开更多
Anthocyanins are biosynthesized in the endoplasmic reticulum and stored in vacuoles,and glutathione S-transferase(GST)plays a key role in anthocyanin accumulation.However,little is known about the mechanism of the rol...Anthocyanins are biosynthesized in the endoplasmic reticulum and stored in vacuoles,and glutathione S-transferase(GST)plays a key role in anthocyanin accumulation.However,little is known about the mechanism of the role of GST in this process.We identified a prominent candidate gene,MaGST1,which is highly expressed during the full-bloom stage,in grape hyacinth.MaGST1 rescued the phenotype of the anthocyanin biosynthesis-deficient mutant tt19,indicating that MaGST1 functions in anthocyanin transport.MaGST1-RNAi transgenic petals were generated by stable genetic transformation.We found that MaGST1-RNAi inhibited the accumulation of anthocyanin in petals.Interestingly,in vitro experiments revealed that recombinant MaGST1 increased the water solubilities of cyanidin(Cya),delphinidin 3-O-glucoside(Dp3G),and petunidin 3-O-glucoside(Pt3G).Compared with Dp3G and Pt3G,Cya significantly suppressed the quenching of the intrinsic tryptophan fluorescence of MaGST1 to a lower level,indicating that MaGST1 has a greater affinity for Cya than for Dp3G and Pt3G.Site-directed mutagenesis and anthocyanin water solubility assays revealed that MaGST1 primarily binds to anthocyanin via Ser-68.Furthermore,yeast one-hybrid,dual-luciferase,and GUS staining assays revealed that MaGST1 expression is positively regulated by MaMybA.In summary,our findings reveal the molecular mechanism of anthocyanin transport mediated by MaGST1.展开更多
The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we develope...The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL_(920))and a 13-fold increase in RPA signal(PA_(880)/PA_(705))in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.展开更多
Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by ...Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.展开更多
GSH system plays a role in the control of the redox balance state, anti-oxidation and protecting life from injury of ROS （ reactive oxygen species）. In present paper, the possible GSH system of Chlamydomonas sp. ICE...GSH system plays a role in the control of the redox balance state, anti-oxidation and protecting life from injury of ROS （ reactive oxygen species）. In present paper, the possible GSH system of Chlamydomonas sp. ICE-L has been investigated by evaluating GSH and GSH-related enzymatic responses at different temperatures using spectrophotometer methods. The results showed that the GSH system is correlated positively to low temperature, and other factors but GR are correlated negatively to high temperature. So GSH and GSH-related enzymes play an important role in the adaptation of Antarctic ice microalgae to low temperature.展开更多
Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial ant...Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.展开更多
Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acry...Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear.We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches.Overall,32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection.Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione,cysteine and L-ascorbic acid,and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation.The phosphatidylcholine treatment reduces the expression of cytochrome P4502E1,alleviates the oxidative stress and inflammation of the liver,and stabilizes the content of glutathione,and thus alleviates the disorder of glutathione.Meanwhile,phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol,thereby maintaining metabolic homeostasis of glycerophospholipid.The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure,but not significantly change the levels of mercapturic acid adducts of acrylamide,providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.展开更多
Liver diseases,particularly acute alcoholic liver injury(AALI),drug-induced liver injury(DILI),and hepatocellular carcinoma(HCC),have become global public health issues.Glutathione(GSH),as an important antioxidant,pla...Liver diseases,particularly acute alcoholic liver injury(AALI),drug-induced liver injury(DILI),and hepatocellular carcinoma(HCC),have become global public health issues.Glutathione(GSH),as an important antioxidant,plays a crucial role in the liver,and its changes are closely associated with liver injury and the development of liver cancer.Therefore,accurately monitoring GSH variations is critical for understanding liver injury mechanisms,early diagnosis,and treatment evaluation.However,traditional detection methods suffer from insufficient sensitivity and selectivity.To address these challenges,we developed an innovative DR-Au^(3+)/DR-Pd^(2+)complex probe that can rapidly and sensitively detect GSH through near-infrared(NIR)fluorescence changes.This probe,with the optimal excitation and emission wavelengths of the probe both located in the NIR region,exhibits excellent selectivity and liver-targeting ability,overcoming the imprecision localization problems of traditional methods.In the AALI and DILI models,the optimized DR-Au^(3+)probe enables real-time monitoring of GSH level fluctuations,providing a powerful tool for early diagnosis of liver injury and dynamic evaluation of therapeutic efficacy.In the DILI and HCC models,the DR-Au^(3+)probe enables visualization and quantitative monitoring of the ferroptosis process,offering new perspectives and approaches for targeted therapy research.The DR-Au^(3+)probe we developed pioneers innovative strategies for establishing accurate diagnostic protocols and individualized therapeutic regimens in hepatic injury and hepatocellular carcinoma management.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
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
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] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-prod...[Objective] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-producing strain HSJB1 was isolated from soil, and the biomass for this strain by flask shaking fermentation was 3.87 g/L while the GSH yield was 91.87 mg/L. According to the morphological, physiological and biochemical characteristics of cells, this strain was primarily identified as Saccharomyces cerevisiae. An ethionine-resistant mutant YBS77 was obtained through UV mutagenesis of the original strain HSJB1, and the biomass for this strain by flask shaking fermentation was 7.60 g dry cell weight/L while the GSH yield was 211.96 mg/L. [Conclusion] The biomass of the mutant obtained by breeding is increased by 96.38% than that of the original strain, and the GSH yield of the mutant obtained by breeding is increased by 130.72% than that from the original strain, which indicates that the breeding method is feasible.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: 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
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
Aim:To analyze the role of cytosolic glutathione S-transferases (cGSTs) and membrane-associated cytosolic GSTs (macGSTs) in prostaglandin biosynthesis and to evaluate the possible interaction between glutathione S-tra...Aim:To analyze the role of cytosolic glutathione S-transferases (cGSTs) and membrane-associated cytosolic GSTs (macGSTs) in prostaglandin biosynthesis and to evaluate the possible interaction between glutathione S-transferases (GSTs) and cyclooxygenase (COX) in vitro.Methods:SDS-PAGE analysis was undertaken for characterization of GSTs,thin layer chromatography (TLC) to monitor the effect of GSTs on prostaglandin biosynthesis from arachi- donic acid (AA) and spectrophotometric assays were done for measuring activity levels of COX and GSTs.Results: SDS-PAGE analysis indicates that macGSTs have molecular weights in the range of 25-28 kDa.In a coupled assay involving GSTs,arachidonic acid and cyclooxygenase-1,rat testicular macGSTs produced prostaglandin E2 and F2~, while the cGSTs caused the generation of prostaglandin D2,E2 and F_(2α).In vitro interaction studies on GSTs and COX at the protein level have shown dose-dependent inhibition of COX activity by macGSTs and vice versa.This effect, however,is not seen with cGSTs.The inhibitory effect of COX on macGST activity was relieved with increasing concentrations of reduced glutathione (GSH) but not with 1-chloro 2,4-dinitrobenzene (CDNB).The inhibition of COX by macGSTs,on the other hand,was potentiated by glutathione.Conclusion:We isolated and purified macGSTs and cGSTs from rat testis and analyzed their involvement in prostaglandin biosynthesis.These studies reveal a revers- ible functional interaction between macGSTs and COX in vitro,with possible interactions between them at the GSH binding site of macGSTs.展开更多
基金supported by University Technology Mara(UiTM)under grant number 600-IRMI/FRGS 5/3(273/2019).
文摘Objective:To systematically review the effects of administering metformin and glutathione alone and in coformulation with other compounds on the fertility and reproductive health of diabetic male rodents.Methods:The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA)were followed to conduct this systematic review.Studies published until August 2024 in PubMed,Web of Science,and Scopus databases were searched,identified,screened,and selected for a detailed review.The keywords included metformin,diabetes,reproduction,glutathione,and rodent models.Results:A total of 166 studies were identified,of which 11 met the inclusion criteria and were included in the qualitative synthesis.One additional study was identified through snowballing and citation tracking,bringing the total to 12 studies.The findings indicate that metformin and glutathione,administered alone or in combination with other compounds,improved sperm count,motility,and morphology;restored reproductive hormone levels;reduced oxidative stress markers;and improved testicular histopathology in diabetic male rodents.Conclusions:Coformulation of metformin and glutathione with other compounds was found to be more effective in improving fertility and reproductive parameters in diabetic male rodents compared to mono-administration.However,further studies on the coformulation of metformin and glutathione are needed to confirm their efficacy and elucidate the underlying mechanisms.Study registration:The study protocol was registered in the International Prospective Register of Systematic Reviews(PROSPERO)with registration number CRD42024561820.
基金financially supported by the Sichuan Science and Technology Program(2024YFNH0016,2024NSFSC2072)the earmarked fund for CARS(CARS-45)+2 种基金the National Science Fund for Distinguished Young Scholars of China(32425056)the National Key Research and Development Program of China(2023YFD2400600)Sichuan Innovation Team of National Modern Agricultural Industry Technology System(SCCXTD-2024-15)。
文摘Background Environmental hypoxia is a common phenomenon in aquaculture,which causes gill tissue injury in fish.Glutathione(GSH)is a vital antioxidant in animal tissues,and its levels decrease under hypoxic conditions.However,the effects of glutathione on fish under hypoxic stress remain poorly understood.This study aimed to investigate the impact of glutathione on gill tissue damage in fish under hypoxic stress and explore the underlying mechanisms.Methods Six experimental diets with varying glutathione concentrations.The actual glutathione levels in these diets,measured by high-performance liquid chromatography,were 0.00,145.95,291.90,437.85,583.80,and 729.75 mg/kg,respectively.Fish were fed these diets for 70 d,after which a 96-h hypoxic stress experiment was conducted.The experiment was set up with normoxic and hypoxic groups,in which the dissolved oxygen in the group was 6 mg/L,and that in the group was 1 mg/L.Results This research revealed that glutathione could enhance the growth performance and antioxidant capability of juvenile grass carp while mitigating the structural damage to gill tissues induced by hypoxia stress.Mechanistic investigations further indicated that glutathione mitigated hypoxia-induced oxidative injury in gill tissues and improved their antioxidant capacity.In addition,glutathione attenuated gill apoptosis induced by hypoxia stress.Glutathione also inhibited the initiation,nucleation,elongation,and degradation phases of autophagy,thereby attenuating hypoxia-induced gill autophagy.Moreover,glutathione was found to alleviate hypoxia-induced endoplasmic reticulum stress(ERS)in gills,a response potentially linked to the suppression of PERK,IRE1,and ATF6 signaling pathways.Finally,based on the ROS and PC contents in gill tissue,the optimum glutathione supplementation levels for juvenile grass carp under hypoxia stress were 437.10 and 495.00 mg/kg,respectively.Conclusions In conclusion,our experimental results demonstrated the effectiveness of glutathione in alleviating gill tissue damage caused by hypoxic stress.This study confirms the feasibility and effectiveness of dietary glutathione addition to alleviate hypoxic stress in fish.
基金supported by OHSU Neurology Foundation Funds and NIH Grant R01NS119226 to IM.
文摘Oxidative stress has long been implicated as a driving force in neurodegenerative disease,with studies of human brain tissue and animal models revealing its important role.Parkinson’s disease(PD),in particular,highlights the selective vulnerability of neurons to the insults of reactive oxygen species.The motor symptoms of PD are caused by degeneration of dopamine neurons in the substantia nigra.These neurons experience increased oxidative stress due in part to highly active mitochondria that support their high bioenergetic demand and the generation of reactive oxygen species by dopamine metabolism(Watanabe et al.,2024).
基金financially supported by the Jiangsu Forestry Science and Technology Innovation and Promotion Project(No.LYKJ-Nanjing[2022]02)the Jiangsu Agricultural Science and Technology Innovation Fund(No.CX(23)3090)。
文摘Smart pesticide delivery systems based on stimuli-responsive nanocarriers have attracted considerable attention because of their potential to enhance pesticide efficiency while reducing environmental risks.In this study,a novel p H/glutathione dual-responsive pesticide delivery system was constructed through the synthesis of disulfide-bridged hollow mesoporous organosilica nanospheres(HMONs)via the St??ber method,followed by poly(acrylic acid)(PAA)coating through distillation-precipitation polymerization to form HMONs@PAA nanocomposites.The resulting abamectin-loaded system(Abamectin-HMONs@PAA)demonstrated a 12.73% pesticide loading capacity and significantly improved photostability,retaining twice as much active ingredient as free abamectin after 250 h of UV irradiation(36 W).Release studies revealed p H-and glutathione-dependent characteristics,with cumulative releases in acidic conditions exceeding those in neutral and alkaline environments by 18.66% and 40.98%,respectively,and a 14.2% increase in glutathione-containing solution(0.2 mmol·L^(-1) in 70% ethanol)after 97 h.Bioassays showed superior performance against Plutella xylostella,with a 13.33% reduction in survival rate compared to conventional suspension at equivalent dosage(40 mg·L^(-1)),while maintaining efficacy after extensive rainfall simulation(20 events over 10 days).This study provides a promising approach for developing environmentally responsive nanopesticides with enhanced durability and controlled-release properties,offering significant potential for sustainable crop protection.
基金supported by the National Natural Science Foundation of China(Grant No.32171863).
文摘Anthocyanins are biosynthesized in the endoplasmic reticulum and stored in vacuoles,and glutathione S-transferase(GST)plays a key role in anthocyanin accumulation.However,little is known about the mechanism of the role of GST in this process.We identified a prominent candidate gene,MaGST1,which is highly expressed during the full-bloom stage,in grape hyacinth.MaGST1 rescued the phenotype of the anthocyanin biosynthesis-deficient mutant tt19,indicating that MaGST1 functions in anthocyanin transport.MaGST1-RNAi transgenic petals were generated by stable genetic transformation.We found that MaGST1-RNAi inhibited the accumulation of anthocyanin in petals.Interestingly,in vitro experiments revealed that recombinant MaGST1 increased the water solubilities of cyanidin(Cya),delphinidin 3-O-glucoside(Dp3G),and petunidin 3-O-glucoside(Pt3G).Compared with Dp3G and Pt3G,Cya significantly suppressed the quenching of the intrinsic tryptophan fluorescence of MaGST1 to a lower level,indicating that MaGST1 has a greater affinity for Cya than for Dp3G and Pt3G.Site-directed mutagenesis and anthocyanin water solubility assays revealed that MaGST1 primarily binds to anthocyanin via Ser-68.Furthermore,yeast one-hybrid,dual-luciferase,and GUS staining assays revealed that MaGST1 expression is positively regulated by MaMybA.In summary,our findings reveal the molecular mechanism of anthocyanin transport mediated by MaGST1.
基金supported by the National Natural Science Foundation of China(Nos.82372116,U23A2097)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010620)+2 种基金Shenzhen Medical Research Fund(Nos.B2302047,A2302047)Shenzhen Science and Technology Program(No.JCYJ20220818095806014)Research Team Cultivation Program of Shenzhen University(No.2023QNT019).
文摘The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL_(920))and a 13-fold increase in RPA signal(PA_(880)/PA_(705))in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.
基金supported by the Department of Education of Guangdong Province (No.2023KTSCX024)the Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20251091)+3 种基金the Joint Funds of the National Natural Science Foundation of China (No.U22A20368)the Key-Area Research and Development Program of Guangdong Province (No.2020B1111100004)Guangdong Basic and Applied Basic Research Foundation (No.2020B1515130005)Shenzhen Baoan District Science and Technology Innovation Bureau Project(Nos.2022JD226 and 2023JD252)。
文摘Colorectal cancer(CRC), one of the leading causes of cancer-related mortality globally, urgently requires complementary and alternative therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Dendrobium officinale(D. officinale), a renowned traditional Chinese medicinal herb, is widely used in several Asian countries for its nutritional and therapeutic benefits.Although D. officinale has demonstrated anti-tumor effects, the molecular mechanisms underlying its action against CRC remain incompletely characterized. This study aimed to elucidate the role of D. officinale in suppressing CRC through the induction of ferroptosis and its regulatory effects on glutathione peroxidase 4(GPX4), a key suppressor of ferroptosis. In vitro assays were conducted using HCT116 and SW480 CRC cell lines, and in vivo efficacy was evaluated in BALB/c nude mice bearing CRC xenografts. D. officinale significantly reduced CRC cell viability and proliferation in vitro and suppressed tumor growth in vivo. Induction of ferroptosis was evidenced by elevated levels of Fe^(2+), malondialdehyde(MDA), and lipid peroxidation, along with a depleted glutathione/oxidized glutathione disulfide(GSH/GSSG) ratio. Notably, these effects were reversed by ferroptosis inhibitors, including ferrostatin-1(Fer-1) and deferoxamine. Consistently, D. officinale markedly downregulated GPX4 expression. Overexpression of GPX4 rescued D. officinale-induced ferroptosis, whereas GPX4 silencing exacerbated this effect. D. officinale suppresses CRC by triggering GPX4-dependent ferroptosis,providing a novel, naturally derived therapeutic approach. These findings bridge traditional medicine and modern oncology, establishing a foundation for developing targeted CRC treatments.
文摘GSH system plays a role in the control of the redox balance state, anti-oxidation and protecting life from injury of ROS （ reactive oxygen species）. In present paper, the possible GSH system of Chlamydomonas sp. ICE-L has been investigated by evaluating GSH and GSH-related enzymatic responses at different temperatures using spectrophotometer methods. The results showed that the GSH system is correlated positively to low temperature, and other factors but GR are correlated negatively to high temperature. So GSH and GSH-related enzymes play an important role in the adaptation of Antarctic ice microalgae to low temperature.
文摘Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.
基金supported by the National Natural Science Foundation of China(21976156)。
文摘Acrylamide is classified as a Class 2A carcinogen and mainly metabolized to produce hepatotoxicity.Phosphatidylcholine is thought to protect the liver from damage,but the protective role of phosphatidylcholine on acrylamide-exposed metabolic disorders remains unclear.We investigated protective effect of phosphatidylcholine on the hepatic metabolism in rats exposed to acrylamide using metabolomics and molecular biology approaches.Overall,32 endogenous effect biomarkers and 4 exposure biomarkers were identified as differential signature metabolites responsible for acrylamide exposure and phosphatidylcholine protection.Acrylamide exposure interferes with glutathione metabolism by consuming antioxidant glutathione,cysteine and L-ascorbic acid,and disrupts lipid and carbohydrate metabolism through reducing carnitine content and increasing lipid peroxidation.The phosphatidylcholine treatment reduces the expression of cytochrome P4502E1,alleviates the oxidative stress and inflammation of the liver,and stabilizes the content of glutathione,and thus alleviates the disorder of glutathione.Meanwhile,phosphatidylcholine shifted acrylamide-induced phosphatidylcholine into lysophosphatidylcholine to storage from lysophosphatidylcholine to diacylglycerol,thereby maintaining metabolic homeostasis of glycerophospholipid.The results suggested that phosphatidylcholine supplementation alleviate the disorder of glutathione and lipid metabolism caused by acrylamide exposure,but not significantly change the levels of mercapturic acid adducts of acrylamide,providing the evidence for phosphatidylcholine protection against acrylamide-induced liver injury.
基金financial support from the National Natural Science Foundation of China(No.21705120)Natural Science Foundation of Shandong Province,China(Nos.ZR2023MB001,ZR2017LB016,ZR2022QB165)+1 种基金Special Fund for Taishan Scholar Project(Nos.tsqn202211231,tsqn202211233)Foundation of Yuandu Scholar and Science and Technology Development Plan Project of Weifang(No.2024JZ0012)。
文摘Liver diseases,particularly acute alcoholic liver injury(AALI),drug-induced liver injury(DILI),and hepatocellular carcinoma(HCC),have become global public health issues.Glutathione(GSH),as an important antioxidant,plays a crucial role in the liver,and its changes are closely associated with liver injury and the development of liver cancer.Therefore,accurately monitoring GSH variations is critical for understanding liver injury mechanisms,early diagnosis,and treatment evaluation.However,traditional detection methods suffer from insufficient sensitivity and selectivity.To address these challenges,we developed an innovative DR-Au^(3+)/DR-Pd^(2+)complex probe that can rapidly and sensitively detect GSH through near-infrared(NIR)fluorescence changes.This probe,with the optimal excitation and emission wavelengths of the probe both located in the NIR region,exhibits excellent selectivity and liver-targeting ability,overcoming the imprecision localization problems of traditional methods.In the AALI and DILI models,the optimized DR-Au^(3+)probe enables real-time monitoring of GSH level fluctuations,providing a powerful tool for early diagnosis of liver injury and dynamic evaluation of therapeutic efficacy.In the DILI and HCC models,the DR-Au^(3+)probe enables visualization and quantitative monitoring of the ferroptosis process,offering new perspectives and approaches for targeted therapy research.The DR-Au^(3+)probe we developed pioneers innovative strategies for establishing accurate diagnostic protocols and individualized therapeutic regimens in hepatic injury and hepatocellular carcinoma management.
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).
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.
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 Scientific Research Project of Liaoning Educational Department(20060154)Initial Funds for Doctors in Dalian Nationalities University(20066206)~~
文摘[Objective] The aim of this study was to screen Saccharomyces for glutathione over-production. [Method] Ethionine-resistant mutants were obtained through UV mutagenesis and rational screening. [Result] A high GSH-producing strain HSJB1 was isolated from soil, and the biomass for this strain by flask shaking fermentation was 3.87 g/L while the GSH yield was 91.87 mg/L. According to the morphological, physiological and biochemical characteristics of cells, this strain was primarily identified as Saccharomyces cerevisiae. An ethionine-resistant mutant YBS77 was obtained through UV mutagenesis of the original strain HSJB1, and the biomass for this strain by flask shaking fermentation was 7.60 g dry cell weight/L while the GSH yield was 211.96 mg/L. [Conclusion] The biomass of the mutant obtained by breeding is increased by 96.38% than that of the original strain, and the GSH yield of the mutant obtained by breeding is increased by 130.72% than that from the original strain, which indicates that the breeding method is feasible.
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.
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.
文摘Aim:To analyze the role of cytosolic glutathione S-transferases (cGSTs) and membrane-associated cytosolic GSTs (macGSTs) in prostaglandin biosynthesis and to evaluate the possible interaction between glutathione S-transferases (GSTs) and cyclooxygenase (COX) in vitro.Methods:SDS-PAGE analysis was undertaken for characterization of GSTs,thin layer chromatography (TLC) to monitor the effect of GSTs on prostaglandin biosynthesis from arachi- donic acid (AA) and spectrophotometric assays were done for measuring activity levels of COX and GSTs.Results: SDS-PAGE analysis indicates that macGSTs have molecular weights in the range of 25-28 kDa.In a coupled assay involving GSTs,arachidonic acid and cyclooxygenase-1,rat testicular macGSTs produced prostaglandin E2 and F2~, while the cGSTs caused the generation of prostaglandin D2,E2 and F_(2α).In vitro interaction studies on GSTs and COX at the protein level have shown dose-dependent inhibition of COX activity by macGSTs and vice versa.This effect, however,is not seen with cGSTs.The inhibitory effect of COX on macGST activity was relieved with increasing concentrations of reduced glutathione (GSH) but not with 1-chloro 2,4-dinitrobenzene (CDNB).The inhibition of COX by macGSTs,on the other hand,was potentiated by glutathione.Conclusion:We isolated and purified macGSTs and cGSTs from rat testis and analyzed their involvement in prostaglandin biosynthesis.These studies reveal a revers- ible functional interaction between macGSTs and COX in vitro,with possible interactions between them at the GSH binding site of macGSTs.
