Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focu...Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.展开更多
Methionine oxidation to methionine sulfoxide （MetSO） is reversed by two types of methionine sulfoxide reducrases （MSRs）, A and B, specific to the S- and R-diastereomers of MetSO, respectively. MSR genes are found ...Methionine oxidation to methionine sulfoxide （MetSO） is reversed by two types of methionine sulfoxide reducrases （MSRs）, A and B, specific to the S- and R-diastereomers of MetSO, respectively. MSR genes are found in most organisms from bacteria to human. In the current review, we first compare the organization of the MSR gene families in photosynthetic organisms from cyanobacteria to higher plants. The analysis reveals that MSRs constitute complex families in higher plants, bryophytes, and algae compared to cyanobacteria and all non-photosynthetic organisms. We also perform a classification, based on gene number and structure, position of redox-active cysteines and predicted sub-cellular localization. The various catalytic mechanisms and potential physiological electron donors involved in the regeneration of MSR activity are then de- scribed. Data available from higher plants reveal that MSRs fulfill an essential physiological function during environmental constraints through a role in protein repair and in protection against oxidative damage. Taking into consideration the ex- pression patterns of MSR genes in plants and the known roles of these genes in non-photosynthetic cells, other functions of MSRs are discussed during specific developmental stages and ageing in photosynthetic organisms.展开更多
This study was designed to compare the effect of methionine(Met)sources(DL-methionine[DLM]and DL-2-hydroxy-4-methylthio-butanoic acid(HMTBa))and their supplementation levels on broiler growth performance and redox sta...This study was designed to compare the effect of methionine(Met)sources(DL-methionine[DLM]and DL-2-hydroxy-4-methylthio-butanoic acid(HMTBa))and their supplementation levels on broiler growth performance and redox state.A 2 x 2 factorial arrangement was used with 2 sources(DLM and HMTBa)and 2 supplementation levels(0.05% and 0.252%)of Met.A total of 480 one-day-old broiler chicks were randomly divided into 4 treatments with 8 replicates per treatment(15 birds per replicate).The experiment lasted for 21 d.Broiler growth performance,redox capacity,redox-related genes expression,and Met transporters in different tissues were tested.Broilers fed high Met supplementation levels had improved(P<0.05)body weight(BW).average daily gain(ADG)and feed conversion ratio(FCR).Similarly,broilers fed high Met levels had better(P<0.05)antioxidant abilities in the serum,small intestine,and liver.Whereas,interactive effects(P<0.05)were also observed between Met sources and levels.Compared with DLM.birds fed HMTBa diets had decreased(P<0.05)total glutathione(T-GSH)and oxidized glutathione(GSSG)contents in duodenum,ileum,and liver.Similarly,broilers fed HMTBa supplemented diets had increased(P<0.05)thioredoxin(Trx)gene expression in the duodenum and ileum,but decreased(P<0.05)glutaredoxin(Grx).glutathione reductase(CSR).and glutathione synthetase(GSS)genes expression.Furthermore,lower gene expression of Na+ and Cl-dependent neutral and cationic amino acid transporter(ATB0,+).and Na+ dependent neutral amino acid transporter(B0 AT)in the duodenum brush border,but higher gene expression of diamine acetyltransferase 1(SAT1)and Na+-independent branched-chain and aromatic amino acid transporter(LAT1)in the jejunum and ileum basement membrane along with higher expression of the proton dependent monocarboxylate transporter 1(MCT1)gene in the ileum were detected in birds fed HMTBa diets.In conclusion.DLM can be effectively used in glutathione synthesis to exert antioxidant functions,whereas HMTBa favors S-adenosylmethionine(SAM)synthesis and t展开更多
This research provides, to the authors’ knowledge, the first integrative model of oxidative stress and C1 metabolism in plants. Increased oxidative stress can cause irreversible damage to photosynthetic components an...This research provides, to the authors’ knowledge, the first integrative model of oxidative stress and C1 metabolism in plants. Increased oxidative stress can cause irreversible damage to photosynthetic components and is harmful to plants. Perturbations at the genetic level may increase oxidative stress and upregulate antioxidant systems in plants. One of the key mechanisms involved in oxidative stress regulation is the ascorbate-glutathione cycle which operates in chloroplasts as well as the mitochondria and is responsible for removal of reactive oxygen species (ROS) generated during photosynthetic operations and respiration. In this research, the complexity of molecular pathway systems of oxidative stress is modeled and then integrated with a previously developed in silico model of C1 metabolism system. This molecular systems integration provides two important results: 1) demonstration of the scalability of the CytoSolve®?Collaboratory™, a computational systems biology platform that allows for modular integration of molecular pathway models, by coupling the in silico model of oxidative stress with the in silico model of C1 metabolism, and 2) derivation of new insights on the effects of oxidative stress on C1 metabolism relative to formaldehyde (HCHO), a toxic molecule, and glutathione (GSH), an important indicator of oxidative homeostasis in living systems. Previous in silico modeling of C1 metabolism, without oxidative stress, observed complete removal of formaldehyde via formaldehyde detoxification pathway and no change in glutathione concentrations. The results from this research of integrative oxidative stress with C1 metabolism, however, demonstrate significant upregulation of formaldehyde concentrations, with concomitant downregulation and depletion of glutathione. Sensitivity analysis indicates that kGSH-HCHO, the rate constant of GSH-HCHO binding, VSHMT, the rate of formation of sarcosine from glycine, and , the rate of superoxide formation significantly affect formaldehyde homeostasis in the 展开更多
Safety assessment of genetically modified organisms (GMOs) is a contentious topic. Proponents of GMOs assert that GMOs are safe since the FDA’s policy of substantial equivalence considers GMOs “equivalent” to their...Safety assessment of genetically modified organisms (GMOs) is a contentious topic. Proponents of GMOs assert that GMOs are safe since the FDA’s policy of substantial equivalence considers GMOs “equivalent” to their non-GMO counterparts, and argue that genetic modification (GM) is simply an extension of a “natural” process of plant breeding, a form of “genetic modification”, though done over longer time scales. Anti-GMO activists counter that GMOs are unsafe since substantial equivalence is unscientific and outdated since it originates in the 1970s to assess safety of medical devices, which are not comparable to the complexity of biological systems, and contend that targeted GM is not plant breeding. The heart of the debate appears to be on the methodology used to determine criteria for substantial equivalence. Systems biology, which aims to understand complexity of the whole organism, as a system, rather than just studying its parts in a reductionist manner, may provide a framework to determine appropriate criteria, as it recognizes that GM, small or large, may affect emergent properties of the whole system. Herein, a promising computational systems biology method couples known perturbations on five biomolecules caused by the CP4 EPSPS GM of Glycine max L. (soybean), with an integrative model of C1 metabolism and oxidative stress (two molecular systems critical to plant function). The results predict significant accumulation of formaldehyde and concomitant depletion of glutathione in the GMO, suggesting how a “small” and single GM creates “large” and systemic perturbations to molecular systems equilibria. Regulatory agencies, currently reviewing rules for GMO safety, may wish to adopt a systems biology approach using a combination of in silico, computational methods used herein, and subsequent targeted experimental in vitro and in vivo designs, to develop a systems understanding of “equivalence” using biomarkers, such as formaldehyde and glutathione, which predict metabolic disruptions, 展开更多
Studies were carried out to determine the activity of complexes of the essential amino acids DL-Lysine and L-Methionine with heavy metals in the oxidation of cyclohexene with tert-butylhydroperoxide in toluene at 80&#...Studies were carried out to determine the activity of complexes of the essential amino acids DL-Lysine and L-Methionine with heavy metals in the oxidation of cyclohexene with tert-butylhydroperoxide in toluene at 80°C. All complexes were prepared through interaction of metal ions and DL-Lysine and L-Methionine at room temperature in aqueous solutions. Only the complexes of Mo and W were obtained from acidic aqueous solution. These complexes were characterized by FT-IR, Moessbauer spectroscopy and EPR analysis. The products of the oxidation reactions were identified by GC/MS analysis. The complexes of Mo and V showed the best activity in the epoxidation reaction of cyclohexene in comparison with other complexes, such as Ni, Mn, Zn, Co, Cu, Cr, Fe and W. Using semi-empirical quantum-chemistry methods, the full energy of the Mo complexes was calculated and their probable structure is presented.展开更多
Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk...Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk production,and thus the nutritional requirements need to be re-evaluated.The current study was conducted to investigate the effects of dietary methionine to lysine(Met:Lys)ratios on the performance of and methionine metabolism in lactating sows.Results:During the 1st week of lactation,piglets reared on sows in the 0.37 to 0.57 Met:Lys ratio groups grew faster than those reared on sows in the control group(0.27)(P<0.01).The 0.37-ratio group showed increased levels of GSHPx in plasma during lactation(P<0.01)and decreased concentrations of urea nitrogen in the plasma of sows(P<0.05).Compared with the 0.27-ratio group,the levels of T-AOC and GSH-Px in the plasma and homocysteine in the milk of lactating sows were significantly increased in sows in the 0.47-ratio group(P<0.01).In sows fed a 0.57-ratio diet,the levels of glutathione and taurine in the plasma and milk were improved significantly during lactation.However,the content of TBARS in the blood(P<0.05 at day 7 and P=0.06 at weaning day)was increased(P<0.01).Moreover,there were linear increases in the levels of homocysteine in the blood and milk of sows during the lactation period(P<0.01)with increased dietary Met:Lys ratios in the lactation diet.Conclusions:The current study indicated that increasing the dietary Met:Lys ratio(0.37~0.57)in the lactation diet had no significant effect on the overall performance of sows or the colostrum and milk composition,but it increased piglet mean BW and piglet ADG during the first week of lactation.Increasing dietary methionine levels had no significant effect on antioxidant function in lactation sows,even though it increased levels of GSH and GSH-Px in the plasma of sows during lactation.However,the content of homocysteine in the plasma and milk increased during lactation due to a high level of dietary methion展开更多
S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death...S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.展开更多
Objective:The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens(GPAE)against nonalcoholic steatohepatitis(NASH)in mice and NCTC-1469 cells.Methods:C57 BL/6 J mice were ...Objective:The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens(GPAE)against nonalcoholic steatohepatitis(NASH)in mice and NCTC-1469 cells.Methods:C57 BL/6 J mice were fed with methionine and choline-deficient(MCD)diet and administered simultaneously with GPAE(500 and 1000 mg/kg/d,respectively)by gavage for six weeks.The biomarkers of NASH in serum and liver were determined.NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid(PA)plus 0.5 mmol/L oleic acid(OA)for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR(Ad-sh CFLAR)for 24 h and then treated with GPAE(80 and 160μg/m L,respectively)for 24 h,and the content of cellular biomarkers of NASH was detected.Results:In mice treated with MCD,GPAE could decrease the levels of serum ALT,AST,the content of hepatic TG,TC and MDA,repress the activities and protein expression of CYP2 E1 and CYP4 A and the phosphorylation of JNK,increase the activities of HO-1,CAT and GSH-Px,up-regulate the m RNA expression of PPARα,FABP5,CPT1α,ACOX,SCD-1,mGPAT,MTTP and the protein expression of CFLAR and NRF2.In NCTC-1469 cells treated with PA and OA,GPAE could decrease the content of cellular TG and ROS,promote the uptake of 2-NBDG,up-regulate the protein expression of CFLAR and NRF2.In NCTC-1469 cells treated with Ad-sh CFLAR,GPAE up-regulated the mRNA and protein expression of CFLAR,down-regulated the phosphorylation of JNK,and increased the protein expression of NRF2 and p IRS1.Conclusion:These results indicated that the activation on CFLAR-JNK pathway might be the main antiNASH mechanism of GPAE,which on the one hand promote theβ-oxidation and efflux of fatty acids in liver,and finally reduce hepatic lipid accumulation,on the other hand increase the activities of antioxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2,and therefore attenuates hepatic oxidative stress damage.展开更多
文摘Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.
文摘Methionine oxidation to methionine sulfoxide （MetSO） is reversed by two types of methionine sulfoxide reducrases （MSRs）, A and B, specific to the S- and R-diastereomers of MetSO, respectively. MSR genes are found in most organisms from bacteria to human. In the current review, we first compare the organization of the MSR gene families in photosynthetic organisms from cyanobacteria to higher plants. The analysis reveals that MSRs constitute complex families in higher plants, bryophytes, and algae compared to cyanobacteria and all non-photosynthetic organisms. We also perform a classification, based on gene number and structure, position of redox-active cysteines and predicted sub-cellular localization. The various catalytic mechanisms and potential physiological electron donors involved in the regeneration of MSR activity are then de- scribed. Data available from higher plants reveal that MSRs fulfill an essential physiological function during environmental constraints through a role in protein repair and in protection against oxidative damage. Taking into consideration the ex- pression patterns of MSR genes in plants and the known roles of these genes in non-photosynthetic cells, other functions of MSRs are discussed during specific developmental stages and ageing in photosynthetic organisms.
基金supported by Beijing Technology Program[Z181100009318008]Beijing Agricultural Innovation Consortium(BAlC04-2018)
文摘This study was designed to compare the effect of methionine(Met)sources(DL-methionine[DLM]and DL-2-hydroxy-4-methylthio-butanoic acid(HMTBa))and their supplementation levels on broiler growth performance and redox state.A 2 x 2 factorial arrangement was used with 2 sources(DLM and HMTBa)and 2 supplementation levels(0.05% and 0.252%)of Met.A total of 480 one-day-old broiler chicks were randomly divided into 4 treatments with 8 replicates per treatment(15 birds per replicate).The experiment lasted for 21 d.Broiler growth performance,redox capacity,redox-related genes expression,and Met transporters in different tissues were tested.Broilers fed high Met supplementation levels had improved(P<0.05)body weight(BW).average daily gain(ADG)and feed conversion ratio(FCR).Similarly,broilers fed high Met levels had better(P<0.05)antioxidant abilities in the serum,small intestine,and liver.Whereas,interactive effects(P<0.05)were also observed between Met sources and levels.Compared with DLM.birds fed HMTBa diets had decreased(P<0.05)total glutathione(T-GSH)and oxidized glutathione(GSSG)contents in duodenum,ileum,and liver.Similarly,broilers fed HMTBa supplemented diets had increased(P<0.05)thioredoxin(Trx)gene expression in the duodenum and ileum,but decreased(P<0.05)glutaredoxin(Grx).glutathione reductase(CSR).and glutathione synthetase(GSS)genes expression.Furthermore,lower gene expression of Na+ and Cl-dependent neutral and cationic amino acid transporter(ATB0,+).and Na+ dependent neutral amino acid transporter(B0 AT)in the duodenum brush border,but higher gene expression of diamine acetyltransferase 1(SAT1)and Na+-independent branched-chain and aromatic amino acid transporter(LAT1)in the jejunum and ileum basement membrane along with higher expression of the proton dependent monocarboxylate transporter 1(MCT1)gene in the ileum were detected in birds fed HMTBa diets.In conclusion.DLM can be effectively used in glutathione synthesis to exert antioxidant functions,whereas HMTBa favors S-adenosylmethionine(SAM)synthesis and t
文摘This research provides, to the authors’ knowledge, the first integrative model of oxidative stress and C1 metabolism in plants. Increased oxidative stress can cause irreversible damage to photosynthetic components and is harmful to plants. Perturbations at the genetic level may increase oxidative stress and upregulate antioxidant systems in plants. One of the key mechanisms involved in oxidative stress regulation is the ascorbate-glutathione cycle which operates in chloroplasts as well as the mitochondria and is responsible for removal of reactive oxygen species (ROS) generated during photosynthetic operations and respiration. In this research, the complexity of molecular pathway systems of oxidative stress is modeled and then integrated with a previously developed in silico model of C1 metabolism system. This molecular systems integration provides two important results: 1) demonstration of the scalability of the CytoSolve®?Collaboratory™, a computational systems biology platform that allows for modular integration of molecular pathway models, by coupling the in silico model of oxidative stress with the in silico model of C1 metabolism, and 2) derivation of new insights on the effects of oxidative stress on C1 metabolism relative to formaldehyde (HCHO), a toxic molecule, and glutathione (GSH), an important indicator of oxidative homeostasis in living systems. Previous in silico modeling of C1 metabolism, without oxidative stress, observed complete removal of formaldehyde via formaldehyde detoxification pathway and no change in glutathione concentrations. The results from this research of integrative oxidative stress with C1 metabolism, however, demonstrate significant upregulation of formaldehyde concentrations, with concomitant downregulation and depletion of glutathione. Sensitivity analysis indicates that kGSH-HCHO, the rate constant of GSH-HCHO binding, VSHMT, the rate of formation of sarcosine from glycine, and , the rate of superoxide formation significantly affect formaldehyde homeostasis in the
文摘Safety assessment of genetically modified organisms (GMOs) is a contentious topic. Proponents of GMOs assert that GMOs are safe since the FDA’s policy of substantial equivalence considers GMOs “equivalent” to their non-GMO counterparts, and argue that genetic modification (GM) is simply an extension of a “natural” process of plant breeding, a form of “genetic modification”, though done over longer time scales. Anti-GMO activists counter that GMOs are unsafe since substantial equivalence is unscientific and outdated since it originates in the 1970s to assess safety of medical devices, which are not comparable to the complexity of biological systems, and contend that targeted GM is not plant breeding. The heart of the debate appears to be on the methodology used to determine criteria for substantial equivalence. Systems biology, which aims to understand complexity of the whole organism, as a system, rather than just studying its parts in a reductionist manner, may provide a framework to determine appropriate criteria, as it recognizes that GM, small or large, may affect emergent properties of the whole system. Herein, a promising computational systems biology method couples known perturbations on five biomolecules caused by the CP4 EPSPS GM of Glycine max L. (soybean), with an integrative model of C1 metabolism and oxidative stress (two molecular systems critical to plant function). The results predict significant accumulation of formaldehyde and concomitant depletion of glutathione in the GMO, suggesting how a “small” and single GM creates “large” and systemic perturbations to molecular systems equilibria. Regulatory agencies, currently reviewing rules for GMO safety, may wish to adopt a systems biology approach using a combination of in silico, computational methods used herein, and subsequent targeted experimental in vitro and in vivo designs, to develop a systems understanding of “equivalence” using biomarkers, such as formaldehyde and glutathione, which predict metabolic disruptions,
文摘Studies were carried out to determine the activity of complexes of the essential amino acids DL-Lysine and L-Methionine with heavy metals in the oxidation of cyclohexene with tert-butylhydroperoxide in toluene at 80°C. All complexes were prepared through interaction of metal ions and DL-Lysine and L-Methionine at room temperature in aqueous solutions. Only the complexes of Mo and W were obtained from acidic aqueous solution. These complexes were characterized by FT-IR, Moessbauer spectroscopy and EPR analysis. The products of the oxidation reactions were identified by GC/MS analysis. The complexes of Mo and V showed the best activity in the epoxidation reaction of cyclohexene in comparison with other complexes, such as Ni, Mn, Zn, Co, Cu, Cr, Fe and W. Using semi-empirical quantum-chemistry methods, the full energy of the Mo complexes was calculated and their probable structure is presented.
基金financially supported by the National Key Research and Development Project of China(NO.2018YFD0501003)China Agriculture Research System(NO.CARS-36)+1 种基金Hubei Provincial Creative Team Project of Agricultural Science and Technology(No.2007–620)Fundamental Research Funds for the Central Universities of China(NO.2662017PY017).
文摘Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk production,and thus the nutritional requirements need to be re-evaluated.The current study was conducted to investigate the effects of dietary methionine to lysine(Met:Lys)ratios on the performance of and methionine metabolism in lactating sows.Results:During the 1st week of lactation,piglets reared on sows in the 0.37 to 0.57 Met:Lys ratio groups grew faster than those reared on sows in the control group(0.27)(P<0.01).The 0.37-ratio group showed increased levels of GSHPx in plasma during lactation(P<0.01)and decreased concentrations of urea nitrogen in the plasma of sows(P<0.05).Compared with the 0.27-ratio group,the levels of T-AOC and GSH-Px in the plasma and homocysteine in the milk of lactating sows were significantly increased in sows in the 0.47-ratio group(P<0.01).In sows fed a 0.57-ratio diet,the levels of glutathione and taurine in the plasma and milk were improved significantly during lactation.However,the content of TBARS in the blood(P<0.05 at day 7 and P=0.06 at weaning day)was increased(P<0.01).Moreover,there were linear increases in the levels of homocysteine in the blood and milk of sows during the lactation period(P<0.01)with increased dietary Met:Lys ratios in the lactation diet.Conclusions:The current study indicated that increasing the dietary Met:Lys ratio(0.37~0.57)in the lactation diet had no significant effect on the overall performance of sows or the colostrum and milk composition,but it increased piglet mean BW and piglet ADG during the first week of lactation.Increasing dietary methionine levels had no significant effect on antioxidant function in lactation sows,even though it increased levels of GSH and GSH-Px in the plasma of sows during lactation.However,the content of homocysteine in the plasma and milk increased during lactation due to a high level of dietary methion
基金Supported by NIH/NIAAA Grants No. AA017425Supported by NIH/NIAAA Grants No. AA018790
文摘S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.
基金supported by the major technological innovation project of Hubei Province(grant No.2016ACA140)the united fund for innovation and entrepreneurship of Ministry of Education of China(grant No.201610512001).
文摘Objective:The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens(GPAE)against nonalcoholic steatohepatitis(NASH)in mice and NCTC-1469 cells.Methods:C57 BL/6 J mice were fed with methionine and choline-deficient(MCD)diet and administered simultaneously with GPAE(500 and 1000 mg/kg/d,respectively)by gavage for six weeks.The biomarkers of NASH in serum and liver were determined.NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid(PA)plus 0.5 mmol/L oleic acid(OA)for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR(Ad-sh CFLAR)for 24 h and then treated with GPAE(80 and 160μg/m L,respectively)for 24 h,and the content of cellular biomarkers of NASH was detected.Results:In mice treated with MCD,GPAE could decrease the levels of serum ALT,AST,the content of hepatic TG,TC and MDA,repress the activities and protein expression of CYP2 E1 and CYP4 A and the phosphorylation of JNK,increase the activities of HO-1,CAT and GSH-Px,up-regulate the m RNA expression of PPARα,FABP5,CPT1α,ACOX,SCD-1,mGPAT,MTTP and the protein expression of CFLAR and NRF2.In NCTC-1469 cells treated with PA and OA,GPAE could decrease the content of cellular TG and ROS,promote the uptake of 2-NBDG,up-regulate the protein expression of CFLAR and NRF2.In NCTC-1469 cells treated with Ad-sh CFLAR,GPAE up-regulated the mRNA and protein expression of CFLAR,down-regulated the phosphorylation of JNK,and increased the protein expression of NRF2 and p IRS1.Conclusion:These results indicated that the activation on CFLAR-JNK pathway might be the main antiNASH mechanism of GPAE,which on the one hand promote theβ-oxidation and efflux of fatty acids in liver,and finally reduce hepatic lipid accumulation,on the other hand increase the activities of antioxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2,and therefore attenuates hepatic oxidative stress damage.
