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.

Theoretical Study on GSH Activation Mechanism of a New Type of Glutathione Transferase Gtt2

Glutathione transferases（GSTs） play an important role in the detoxification of xenobiotic/endobiotic toxic compounds. The α-, π-, and/l-classes of cytosolic GSTs have been studied extensively, while Gtt2 from Saccharo- myces cerevisiae, a novel atypical GST, is still poorly understood. In the present study, we investigated the gluta- thione（GSH） activation mechanism of Gtt2 using the density functional theory（DFT） with the hybrid functional B3LYP. The computational results show that a water molecule could assist a proton transfer between the GSH thiol and the N atom of His133. The energy barrier of proton transfer is 46.0 kJ/mol. The GSH activation mechanism and the characteristics of active site are different from those of classic cytosolic GSTs.

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.

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.

Characterization of the dissociation pathways of dichloromethane and glutathione in dichloromethane dehalogenase

Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.

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.

Induction of Phase II Enzymes Glutathione-S-Transferase and NADPH: Quinone Oxydoreductase 1 with Novel Sulforaphane Derivatives in Human Keratinocytes: Evaluation of the Intracellular GSH Level

Phase II enzymes including NADPH: Quinone Oxydoreductase 1 (NQO1) and Glutathione-S-Transferase (GST) represents a major and natural cellular protection system against deleterious environmental factors which cause skin damages. Sulforaphane is one of the most popular isothiocyanates found in cruciferous vegetables and known for its cytoprotective effects by inducing Phase II enzymes. Five novel sulforaphane derivatives were synthetized and tested for their activity on NQO1 and GST induction as well as for their effect on total GSH intracellular level using colorimetric assays on human keratinocytes cell line (HaCat). As sulforaphane and the synthetized components showed variable toxicity after their evaluation by means of in vitro cytotoxicity (MTT test), cells were treated at a concentration of 5 μM during 48 hours. The results showed that the addition products of sulforaphane decreased cytotoxity but none of those derivatives had a better effect than referenced sulforaphane on Phase II enzymes. It seems that the isothiacyanate function remains important for the sulforaphane activity.

Effects of Cu Contamination on GSH- Px( Glutathione Peroxidase) Activity of Earthworms( Eisenia fetida ) in Soils

[ Objective] This study aimed to investigate the effects of Cu contamination in soils on GSH-Px （ glutathione peroxidase） activity of earthworms （ Eisenia fetida）. [ Method ] By artificial soil contamination method, changes in GSH-Px activity of earthworms under different Cu concentrations were investigated [ Result ] In the early exposure period, low-concentration Cu stress activated GSH-Px activity of earthworms to a certain extent; with the extension of extxqsure time and increase of Cu concentration, GSH-Px activity of earthworms showed a decreasing trend; however, under high-concentration Cu stress, there was no remarkable reg- ularity in the reduction of GSH-Px activity of earthworms. [ Conclusion] This study laid a solid foundation for further revealing the synergistic mechanism of antioxidant enzymes of earthworms.

Toxicity of Nonylphenol on Microcystis aeruginosa Mediated by the Ascorbate-glutathione (AsA-GSH ) Cycle

Nonylphenol( NP) is a stable metabolic product of nonylphenol ethoxylates,which is widely used as an industrial surfactant. NP has been classified as an endocrine disrupter,and its toxicity to organisms can be biomagnified through the food chain. As compared with the endocrine disrupting effect,the toxicity of NP to organisms has not been studied intensively,and the toxicity mechanisms have often been ignored. In the present study,Microcystis aeruginosa,a freshwater alga belonging to the first level of the trophic chain,was chosen to detect the toxicity of NP. The mechanisms of toxicity mediated by the AsA-GSH cycle were explored. The acute toxicity of NP to M. aeruginosa within 96 h was studied and an EC_(50) concentration of 3. 45 mg/L was found. Further,the results showed that the toxicity of NP increased with the increase in concentration and exposure time. As compared with that in the control,the APX and MDHAR activities mostly increased,whereas DHAR activity fluctuated.However,the AsA content elevated at first,but decreased significantly after 72 h. For the GSH system,GR activity was always higher than that in the control. Nevertheless,the reduced GSH content was mostly inhibited. Therefore,the performance of AsA-GSH antioxidant defense system could explain the results of NP toxicity: the enzyme activities and antioxidant molecules increased initially,but an overall decline appeared after exposure for 24 h. This research is helpful for estimating the toxicity of NP integrally and improves people's understanding of mechanisms of NP toxicity in algae.

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。

多枝赖草Glutathione Reductase基因克隆及胁迫表达分析

为了获得完整的谷胱甘肽还原酶基因序列,根据已克隆到的谷胱甘肽还原酶cDNA片段设计引物,利用RACE扩增获得了基因全长序列,应用Southern印迹杂交法分析基因存在状态,Northern印迹杂交法研究基因表达情况.结果表明,该基因全长1580 bp,含一个1 140 bp的开放阅读框架,编码380个氨基酸,与其它植物谷胱甘肽还原酶氨基酸序列的同源性在77%-92%之间;Southern杂交表明该基因有一个拷贝;Northern杂交表明在逆境胁迫下GR基因表达加强.

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.

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.

弱光及干旱条件下AMF对切花月季光合和AsA-GSH循环的影响

旨在探究弱光及干旱条件下丛枝菌根真菌(AMF)对切花月季光合、AsA-GSH循环以及渗透调节物质的影响。盆栽条件下设置100%全光照(L1)、50%全光照(L2)2个光照处理组,80%土壤持水量(W1)和40%土壤持水量(W2)2个水分处理组,接种AMF[变形球囊霉(Glomus versiforme)+异形根孢囊霉(Rhizophagus irregularis)]及不接种对照(CK)共8个处理。结果表明,AMF能够侵染切花月季根系,显著提高切花月季生长品质。弱光和/或干旱胁迫下,与不接种对照相比,接种AMF能有效地促进切花月季叶片的净光合速率(P_(n))、蒸腾速率(T_(r))、气孔导度(G_(s))和水分利用效率(WUE)增加,降低细胞间隙CO_(2)浓度(C_(i));在L2W2处理条件下,与不接种对照相比,接种AMF使切花月季叶片中的抗坏血酸过氧化物酶(APX)、谷胱甘肽还原酶(GR)、单脱氢抗坏血酸还原酶(MDAR)和脱氢抗坏血酸还原酶(DHAR)活性分别提高5.2%、15.4%、21.7%和35.9%;接种AMF的抗坏血酸(AsA)含量与对照处理无显著差异,还原型谷胱甘肽(GSH)含量提高8.1%,GSH/GSSG比值增加7.9%;接种AMF后切花月季丙二醛(MDA)含量显著降低,可溶性糖、可溶性蛋白和脯氨酸(Pro)含量明显增加。结论认为AMF通过维持AsA/DHA和GSH/GSSG的稳定,提高AsA-GSH循环中相关酶活性,增加切花月季叶片可溶性糖、可溶性蛋白和脯氨酸含量而降低MDA含量来适应水分和光照的变化,形成适应光照和水分条件变化的生理生态对策来改善切花月季生长品质。

干旱胁迫下外源褪黑素对王族海棠光合作用、ASA-GSH循环以及激素变化的影响

为探究干旱胁迫下外源褪黑素(MT)对王族海棠(Malus‘Royalty’)生长状况、光合作用、激素代谢以及抗坏血酸-谷胱甘肽(ASA-GSH)循环生理的影响,盆栽条件下设置正常水分(CK)、干旱胁迫(DS)以及干旱胁迫下叶片喷施6个质量分数(50、100、150、200、250、300 mg/kg,分别记为MT1、MT2、MT3、MT4、MT5、MT6)的褪黑素,共8个处理,分析干旱胁迫下不同质量分数褪黑素处理对王族海棠生长量、叶绿素含量、光合参数、激素代谢以及ASA-GSH循环中相关酶活性和抗氧化物质含量的影响。结果表明,与DS处理相比,DS+MT3处理下的株高、基径、总干质量、根系总体积以及根系平均直径分别增加54.7%、20.0%、143.2%、33.5%、6.9%;叶绿素a、叶绿素b以及类胡萝卜素含量分别增加20.5%、115.7%和83.0%;光合参数中净光合速率(Pn)、蒸腾速率(Tr)、气孔导度(Gs)以及水分利用效率(WUE)分别增加51.8%、110.9%、55.5%和96.6%,且Pn恢复至CK水平,胞间CO_(2)浓度(Ci)和气孔限制值(Ls)则分别下降43.3%和57.0%;PSⅡ最大光化学量子效率(Fv/Fm)、PSⅡ潜在活性(Fv/Fo)、PSⅡ实际光化学量子效率(ΦPSⅡ)以及PSⅡ有效光化学量子效率(Fv′/Fm′)分别增加5.4%、61.8%、171.6%和168.7%。王族海棠AsA-GSH循环中抗坏血酸过氧化物酶(APX)、脱氢抗坏血酸还原酶(DHAR)、单脱氢抗坏血酸还原酶(MDHAR)以及谷胱甘肽还原酶(GR)活性分别增加168.3%、90.4%、167.2%和126.0%;抗坏血酸(ASA)含量、谷胱甘肽(GSH)含量、抗坏血酸/脱氢抗坏血酸(ASA/DHA)、还原型/氧化型谷胱甘肽(GSH/GSSG)分别增加102.5%、67.5%、129.8%和342.1%;生长素(IAA)、赤霉素(GA)、玉米素核苷(ZR)含量分别增加26.2%、24.6%和89.3%,脱落酸(ABA)含量降低49.0%。干旱胁迫下,王族海棠的生长参数、光合作用以及ASA-GSH循环过程受到抑制,激素平衡遭到破坏。叶片喷施不同质量分数的褪黑素能够调节内源激素的代谢水平,提高光合作用,增强ASA-GSH循环中相关酶活性以及抗氧化物质含量,促进光合色素的合成和积累,改善叶绿素荧光参数,进而提高植物的生物量,增强王族海棠的抗旱能力,其中以叶片喷施150 mg/kg的褪黑素提高王族海棠的抗旱性效果最好。

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.

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.

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.

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.