Systematic analysis and functional verification of citrus glutathione S-transferases reveals that CsGSTF1 and CsGSTU18contribute negatively to citrus bacterial canker

Citrus bacterial canker(CBC) is resulted from Xanthomonas citri subsp. citri(Xcc) infection and poses a significant threat to citrus production.Glutathione S-transferases(GSTs) are critical in maintaining redox homeostasis in plants, especially in relation to abiotic and biotic stress responses. However, the function of GSTs in resisting CBC remains unclear. Here, citrus glutathione S-transferases were investigated applying a genome-wide approach. In total, 69 CsGSTs belonging to seven classes were identified, and the phylogeny, chromosomal distribution, gene structures and conserved motifs were analyzed. Several CsGSTs responded to Xcc infection, as observed in the upregulation of CsGSTF1 and CsGSTU18 in the CBC-sensitive ‘Wanjincheng' variety but not in the resistant ‘Kumquat' variety. CsGSTF1 and CsGSTU18 were localized at the cytoplasm. Transient overexpression of CsGSTF1 and CsGSTU18 mediated reactive oxygen species(ROS) scavenging, whereas the virus-induced gene silencing(VIGS) of CsGSTF1 and CsGSTU18 caused strong CBC resistance and ROS burst. The present study investigated the characterization of citrus GST gene family, and discovered that CsGSTF1 and CsGSTU18 negatively contributed to CBC through modulating ROS homeostasis. These findings emphasize the significance of GSTs in infection resistance in plants.

Changes of the glutathione redox system during the weaning transition in piglets, in relation to small intestinal morphology and barrier function

Background: Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione(GSH)redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight(LBW) and normal birth weight(NBW) littermates were assigned to one of three weaning treatments;i.e. weaning at 3 weeks of age(3 w), weaning at 4 weeks of age(4 w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age(3 d3 w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.Results: Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status(GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3 d3 w weaned piglets at d 5 postweaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran(FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.Conclusion: Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3 w and 4 w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3 d3 w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.

A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk

Objectives： To investigate the correlation between glutathione S-transferase P1 （GSTP1） Ilel05Val polymorphism and colorectal cancer （CRC） risk. Methods： Studies were identified to investigate the association between GSTP1 Ilel05Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios （OR） and 95% confidence intervals （95 % CI） were used to measure GSTP 1 Ile 105Val polymorphisms and CRC risk. Results： A total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that lie 105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ilel05Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium （HWE） in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results. Conclusions： GSTP1 Ilel05Val might be associated with increased risk of CRC. However, more high- quality case-control studies should be performed to confirm the authenticity of our conclusion.

Yeast One-hybrid System Used to Identify the Binding Proteins for Rat Glutathione S-transferase P Enhancer I

Objective To detect the trans-factors specifically binding to the strong enhancerelement (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. MethodsYeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library toidentify potential trans-factors that can interact with core sequence of GPEI(cGPEI).Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of trans-factors to cGPEI. Results cDNA fragments coding for the C-terminal part of thetranscription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. Thebinding of c-Jun and ANT to GPEI core sequence were confirmed. Conclusions Rat c-juntranscriptional factor and ANT may interact with cGPEI. They could play an important rolein the induced expression of GST-P gene.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

The effect of high fat food on erythrocyte phospholipids, fatty acids composition and glutathione redox-system of rats with alimentary dyslipidemia

To evaluate the effects of high fat food consisted of tallow (19% of total diets) and cholesterol (2%) on modification of erythrocyte phospholipids, fatty acids composition and glutathione redox- system of male Wistar rats with alimentary dysli- pidemia. The results demonstrated that after 30 and 180 days of high-fat feed erythrocyte phos- phatidylinositol and phosphatidylcholine levels were reduced, phosphatidylserine were in-creased. Only on the 90 days of the experiment phosphatidylinositol level increased. In all grow- ups the erythrocyte 18:0 saturated fatty acids and 20:4n6, 22:4n6 polyunsaturated fatty acids (PUFA) were increased. Deficit of n3 PUFA- 20:5n3 and 22:6n3 after 90 and 180 days high fat feed promoted compensatory synthesis from 18:1n9 on 20:3n9. Erythrocyte maleic dialde-hyde increased, glutathione level decreased in all groups of rats after fed with high-fat feed. Glutathione reductase and glutathione peroxi-dase activity decreased in erythrocytes after 30 and 180 days of high-fat feed. In conclusion: high-fat diet during 30-90 days started adaptive answer in lipids of membrane and glutathione redox-system. Important mechanism of adapta-tion of a cellular membrane to high-fat diet is increase major, structuring a membrane phos-phatidylethanolamine and minor, most meta-bolic significant fractions phospholipids (phos- phatidylinositol), keeps homeostasis of 18:2n6 and 22:6n3, 20:3n9 compensatory synthesis, decrease in activity of processes lipid peroxi-dation, activation of enzymes of redox-system glutathione. But prolonging the high-fat feeding (180 days and more) formed failure compensa-tory processes (dysadaptation). It is a risk factor of developmening atherosclerosis, diabetes, steatogepatitis and other diseases.

In-Silico Analysis &In-Vivo Results Concur on Glutathione Depletion in Glyphosate Resistant GMO Soy, Advancing a Systems Biology Framework for Safety Assessment of GMOs

This study advances previous efforts towards development of computational systems biology, in silico, methods for biosafety assessment of genetically modified organisms (GMOs). C1 metabolism is a critical molecular system in plants, fungi, and bacteria. In our previous research, critical molecular systems of C1 metabolism were identified and modeled using CytoSolve?, a platform for in silico analysis. In addition, multiple exogenous molecular systems affecting C1 metabolism such as oxidative stress, shikimic acid metabolism, glutathione biosynthesis, etc. were identified. Subsequent research expanded the C1 metabolism computational models to integrate oxidative stress, suggesting glutathione (GSH) depletion. Recent integration of data from the EPSPS genetic modification of Soy, also known as Roundup Ready Soy (RRS), with C1 metabolism predicts similar GSH depletion and HCHO accumulation in RRS. The research herein incorporates molecular systems of glutathione biosynthesis and glyphosate catabolism to expand the extant in silico models of C1 metabolism. The in silico results predict that Organic Soy will have a nearly 250% greater ratio of GSH and GSSG, a measure of glutathione levels, than in RRS that are glyphosate-treated glyphosate-resistant Soy versus the Organic Soy. These predictions also concur with in vivo greenhouse results. This concurrence suggests that these in silico models of C1 metabolism may provide a viable and validated platform for biosafety assessment of GMOs, and aid in selecting rational criteria for informing in vitro and in vivo efforts to more accurately decide in the problem formulation phase whose parameters need to be assessed so that conclusion on “substantial equivalence” or material difference of a GMO and its non-GMO counterpart can be drawn on a well-grounded basis.

Dietary glycine supplementation enhances syntheses of creatine and glutathione by tissues of hybrid striped bass(Morone saxatilis ♀ × Morone chrysops ♂) fed soybean meal-based diets

Background We recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5-to 40-g(Phase-I)and 110-to 240-g(Phase-II)hybrid striped bass(HSB),as well as their intestinal health.Although glycine serves as an essential substrate for syntheses of creatine and glutathione(GSH)in mammals(e.g.,pigs),little is known about these metabolic pathways or their nutritional regulation in fish.This study tested the hypothesis that glycine supplementation enhances the activities of creatine-and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass(HSB;Morone saxatilis♀×Morone chrysops♂).Methods Phase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%,1%,or 2%glycine for 8 weeks.At the end of the 56-d feeding,tissues(liver,intestine,skeletal muscle,kidneys,and pancreas)were collected for biochemical analyses.Results In contrast to terrestrial mammals and birds,creatine synthesis occurred primarily in skeletal muscle from all HSB.The liver was most active in GSH synthesis among the HSB tissues studied.In Phase-I HSB,supplementation with 1%or 2%glycine increased(P<0.05)concentrations of intramuscular creatine(15%–19%)and hepatic GSH(8%–11%),while reducing(P<0.05)hepatic GSH sulfide(GSSG)/GSH ratios by 14%–15%,compared with the 0-glycine group;there were no differences(P>0.05)in these variables between the 1%and 2%glycine groups.In Phase-II HSB,supplementation with 1%and 2%glycine increased(P<0.05)concentrations of creatine and GSH in the muscle(15%–27%)and liver(11%–20%)in a dose-dependent manner,with reduced ratios of hepatic GSSG/GSH in the 1%or 2%glycine group.In all HSB,supplementation with 1%and 2%glycine dose-dependently increased(P<0.05)activities of intramuscular arginine:glycine amidinotransferase(22%–41%)and hepaticγ-glutamylcysteine synthetase(17%–37%),with elevated activities of intramuscular guanidinoacetate methyltransferase and hepatic GSH synthetase and GSH reductase in the 1%or 2%glycine group.Glycine supplementation also increased(P<0.05)concentrations of creatine and activities of its synthetic enzymes in tail kidneys and pancreas,and concentrations of GSH and activities of its synthetic enzymes in the proximal intestine.Conclusions Skeletal muscle and liver are the major organs for creatine and GSH syntheses in HSB,respectively.Dietary glycine intake regulates creatine and GSH syntheses by both Phase-I and Phase-II HSB in a tissue-specific manner.Based on the metabolic data,glycine is a conditionally essential amino acid for the growing fish.

The effect of glutathione on glucosinolate biosynthesis through the sulfur assimilation pathway in pakchoi associated with the growth conditions

Glucosinolates(GSLs) are a group of nitrogen-and sulfur-containing secondary metabolites, synthesized primarily in members of the Brassicaceae family, that play an important role in food flavor, plant antimicrobial activity, resistance to insect attack, stress tolerance, and human anti-cancer effects. As a sulfur-containing compound, glutathione has a strong connection with GSLs biosynthesis as a sulfur donor or redox system, and exists in reduced(glutathione;GSH) and oxidized(glutathione disulfide;GSSG) forms. However, the mechanism of GSH regulating GSLs biosynthesis remainds unclear. Hence, the exogenous therapy to pakchoi under normal growth condition and sulfur deficiency condition were conducted in this work to explore the relevant mechanism. The results showed that exogenous application of buthionine sulfoximine, an inhibitor of GSH synthesis, decreased the transcript levels of GSLs synthesis-related genes and transcription factors, as well as sulfur assimilation-related genes under the normal growth condition. Application of exogenous GSH inhibited the expression of GSLs synthesis-and sulfur assimilation-related genes under the normal condition, while the GSLs biosynthesis and the sulfur assimilation pathway were activated by exogenous application of GSH when the content of GSH in vivo of plants decreased owing to sulfur deficiency. Moreover,exogenous application of GSSG increased the transcript levels of GSLs synthesis-and sulfur assimilation-related genes under the normal growth condition and under sulfur deficiency. The present work provides new insights into the molecular mechanisms of GSLs biosynthesis underlying glutathione regulation.

Screening of Saccharomyces Strains Highly Producing Glutathione and Breeding of Its Ethionine-resistant Mutants

[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.

双核Pt(Ⅳ)配合物与Guanosine-5′-Monophosphate和Glutathione反应的核磁共振光谱研究(英文)

合成了一个新型的双核Pt(Ⅳ)配合物｛[cis-Pt(NH3)2Cl(OH)2]2(4,4′-methylenedianiline)｝(NO3)2(化合物1)及相应的15N标记化合物｛[cis-Pt(15NH3)2Cl(OH)2]2(4,4′-methylenedianiline)｝(NO3)2(化合物15N-1)。利用1HNMR和ESMS进行了结构表征,化合物15N-1的2D[1H,15N]HSQCNMR发现,该化合物在水溶液中存在同分异构体。2D[1H,15N]HSQCNMR技术跟踪了化合物15N-1与Guanosine-5′-Monophosphate(5′-GMP)和Glutathione(GSH)的反应。结果显示,5′-GMP能在0.5h内将化合物1还原,而GSH在6h以后才能够部分的将化合物1还原。化合物1所表现出来的反应性能将有利于提高其治疗效果和降低毒副作用。

Expression of Presenilin-2 and Glutathione S Transferase π and Their Clinical Significance in Breast Infiltrating Ductal Carcinoma

To investigate the expressions of presenilin-2 (PS2) and glutathione Stransferase π (GSTπ) and their roles in prognosis and therapy of breast infiltrating ductalcarcinoma. Methods: The paraffin-embedded specimens of 210 patients with breast infiltrating ductalcarcinoma were examined by using LSAB immunohistochemistry for the expression of PS2 and GSTπ.Results: The expression rate of PS2 and GSTπ was 49.5% (104/210) and 48.1% (101/210) respectively.The 5-year and 10-year postoperative survival rates in 4 groups, from high to low, were group 1 (PS2positive expression/GSTπ negative expression), group 2 (PS2 positive expression/GSTπ positiveexpression), group 3 (PS2 negative expression/GSTπ negative expression) and group 4 (PS2 negativeexpression/GSTπ positive expression) in turn. Conclusion: The prognosis of the group 1 was thebest, followed by the group 2, group 3 and group 4 in turn. These results suggested that thereasonable use of endocrinotherapy and chemotherapy for patients with breast infiltrating ductalcarcinoma is necessary.

Glutathione S-transferase M1 and T1 Gene Deletion Associated with Increased Susceptibility to Nasopharyngeal Carcinoma

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.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

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.

Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.

Glutamine:aprecursor of glutathione and its effect on liver

AIM To investigate the relationship between alanyl-glutamine (ALA-GLN) and glutathione (GSH) biosynthesis in hepatic protection.METHODS Twenty male Wistar rats were randomly divided into two groups: one receiving standard parenteral nutrition (STD) and the other supplemented with or without ALA-GLN for 7 days. The blood and liver tissue samples were examined after 5-fluorouracil (5-FU) was injected peritoneally.RESULTS The concentration measurements were significantly higher in ALA-GLN group than in STD group in serum GLN (687 μmol/ L±50 μmol/ L vs 505 μmol/ L±39 μmol/ L, P＜0.05), serum GSH (14 μmol/ L±5 μmol/ L vs 7 μmol/ L±3 μmol/ L, P＜0.01) and in liver GSH content (6.9 μmol/ g±2.5 μmol/ g vs 4.4 μmol/ g±1.6 μmol/ g liver tissue, P＜0.05). Rats in ALA-GLN group had lesser elevations in hepatic enzymes after 5-FU administration.CONCLUSION The supplemented nutrition ALA-GLN can protect the liver function through increasing the glutathione biosynthesis and preserving the glutathione stores in hepatic tissue.

Glutathione S-transferases M1,T1 genotypes and the risk of gastric cancer:A case-control study

AIM: Glutathione S-transferases (GSTs) are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione S-transferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTT1 and GSTT1 and gastric cancer. METHODS: A population based case-control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTT1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS: An increase in risk for gastric cancer was found among carriers of GSTT1 null genotype. The adjusted odds ratio (OR) was 2.63 95% Confidence Interval (95% CI) 1.17-5.88, after controlling for age, gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTT1 null and GSTT1 non-null genotype was significantly higher than in those with both GSTT1 and GSTT1 non-null genotype (OR = 2.77, 95% CI 1.15-6.77). Compared with those subjects who never smoked and had normal GSTT1 genotype, ORs were 1.60 (95% CI:0.62-4.19) for never smokers with GSTT1 null type, 2.33 (95% CI 0.88-6.28) for smokers with normal GSTT1, and 8.06 (95% CI 2.83-23.67) for smokers with GSTT1 null type. CONCLUSIONS: GSTT1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinogenesis of gastric cancer.

Cold acclimation improves photosynthesis by regulating the ascorbate–glutathione cycle in chloroplasts of Kandelia obovata

As the most northerly mangrove species in China, Kandelia obovata may undergo extreme cold event stress. Enhancing the cold tolerance of this species is crucial to its successful afforestation. This study aimed to determine the resistance of K. obovata seedlings to low temperature stress by cold acclimation and to explain the mechanisms for alleviating cold injury. To understand these mechanisms, seedlings that were acclimatized and not acclimatized were exposed to 5℃/- 2℃(day/night)for 48 h.Results showed that low temperature stress reduced leaf photosynthesis of non-acclimatized seedlings by inducing oxidative stress and structural damage to chloroplasts. These phenomena were shown by increasing levels of malondialdehyde (MDA), O2-and H2O2, as well as decreasing enzyme activities in the ascorbate–glutathione (AsA-GSH) cycle. However, cold-acclimatized seedlings had improved photosynthetic rates and efficiency of photosystem II (PSII) under low temperature stress. Compared with non-acclimatized seedlings, leaves of coldacclimatized seedlings under low temperature stress for 48 h exhibited higher anti-oxidative enzyme activities, lower levels of O2^- and H2O2, less damage to chloroplast structure, and removed 33.7% of MDA at low temperature stress for 48 h. The data indicate that cold acclimation enhances photosynthetic capacity by effectively regulating activation in the PSII electron transport and the AsA–GSH cycle to scavenge excess ROS in chloroplasts, while the latter is more important.

Response of Glutathione and Glutathione S-transferase in Rice Seedlings Exposed to Cadmium Stress

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.

Exogenous GSH protects tomatoes against salt stress by modulating photosystem Ⅱ efficiency, absorbed light allocation and H2O2-scavenging system in chloroplasts

The effects of exogenous GSH（reduced glutathione）on photosynthetic characteristics,photosystem Ⅱ efficiency,absorbed light energy allocation and the H2O2-scavenging system in chloroplasts of salt-stressed tomato（Solanum lycopersicum L.）seedlings were studied using hydroponic experiments in a greenhouse.Application of exogenous GSH ameliorated saline-induced growth inhibition,the disturbed balance of Na＋ and Cl- ions and Na＋/K＋ ratios,and the reduction of the net photosynthetic rate（Pn）.GSH also increased the maximal photochemical efficiency of PSⅡ（Fv/Fm）,the electron transport rate（ETR）,the photochemical quenching coefficient（qP）,and the non-photochemical quenching coefficient（NPQ）.In addition,GSH application increased the photochemical quantum yield（Y（Ⅱ））and relative deviation from full balance between the photosystems（β/α-1）and decreased the PSⅡ excitation pressure（1-qP）and quantum yield of non-regulated energy dissipation（Y（NO））in leaves of salt-stressed tomatoes without BSO（L-buthionine-sulfoximine,an inhibitor of key GSH synthesis enzymeγ-glutamylcysteine synthetase）or with BSO.Further,the addition of GSH depressed the accumulation of H2O2 and malondialdehyde（MDA）,induced the redistribution of absorbed light energy in PSⅡ reaction centers,and improved the endogenous GSH content,GSH/GSSH ratio and activities of H2O2-scavenging enzymes（including superoxidase dismutase（SOD）,catalase（CAT）,peroxidase（POD）and key enzymes in the AsA-GSH cycle and Grx system）in the chloroplasts of salt-stressed plants with or without BSO.Therefore,GSH application alleviates inhibition of salt-induced growth and photosynthesis mainly by overcoming stomatal limitations,improving the PSⅡ efficiency,and balancing the uneven distribution of light energy to reduce the risk of ROS generation and to mediate chloroplast redox homeostasis and the antioxidant defense system to protect the chloroplasts from oxidative damage.Thus,GSH may be used as a potential tool for alleviating salt stress in tomato plants.