Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related disease...Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related diseases is oxidative stress.In recent years,the importance of H2S has become clear,although its antioxidant function has not yet been fully explored.The enzymes cystathionineβ-synthase,cystathionineγ-lya-se,and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S.Previously,H2S was considered a neuromodulator,given its role in long-term hippocampal potentiation,but it is now also recognized as an antioxidant in age-related neurodegeneration.Due to aerobic metabolism,the central nervous system is vulnerable to oxidative stress in brain aging,resulting in age-associated degenerative diseases.H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes,including superoxide dismutase,catalase,and glutathione peroxidase,which protect against the effects of aging by regulating apoptosis-related genes,including p53,Bax,and Bcl-2.This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and Down syndrome.展开更多
Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s diseas...Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.展开更多
This study aimed to observe changes in the hydrogen sulfide(H_2S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic ...This study aimed to observe changes in the hydrogen sulfide(H_2S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H_2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15 th, 30 th, and 52 nd day. The expression of cystathionine β-synthase(CBS) and cystathionine γ-lyase(CSE) protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction(RT-PCR), respectively. The results indicated that H_2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H_2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mR NA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H_2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H_2S protects vascular remodelling in the liver, and that CSE is indispensable in this process.展开更多
We investigated the expression of hydrogen sulphide (H2S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H2S induces relaxation of human ...We investigated the expression of hydrogen sulphide (H2S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley (SD) rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine β-synthase (CBS), cystathionine y lyase (CSE) and 3-mercaptopyruvate sulphur transferase (MPST, as known as 3-MST) by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine (L-Cys, a substrate of CBS, CSE and MPST) elicited relaxation in a dose-dependent manner on human bladder strips ere-contracted by acetylcholine chloride. This effect could be diminished by the ATe-sensitive potassium ion (KATe) channel blocker glibenclamide (GLB), the CSE inhibitor DL-propargylglycine (PEG) and the CBS inhibitor hydroxylamine (HA). H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms (LUTS) or overactive bladder (OAB).展开更多
Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in di...Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.展开更多
基金supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning, No. 2018R1A2B6001123 (to NYJ), No. 2018R1D1A1B07040282 (to JJ)
文摘Hydrogen sulfide(H2S)is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases.One of the major causes of age-related diseases is oxidative stress.In recent years,the importance of H2S has become clear,although its antioxidant function has not yet been fully explored.The enzymes cystathionineβ-synthase,cystathionineγ-lya-se,and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S.Previously,H2S was considered a neuromodulator,given its role in long-term hippocampal potentiation,but it is now also recognized as an antioxidant in age-related neurodegeneration.Due to aerobic metabolism,the central nervous system is vulnerable to oxidative stress in brain aging,resulting in age-associated degenerative diseases.H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes,including superoxide dismutase,catalase,and glutathione peroxidase,which protect against the effects of aging by regulating apoptosis-related genes,including p53,Bax,and Bcl-2.This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and Down syndrome.
文摘Objective To investigate the relationship of plasma homocysteine (Hcy) levels and the gene polymorphisms of N5, N10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS) with Alzheimer’s disease (AD). Methods Plasma Hcy levels were measured by means of high voltage capillary electrophoresis with ultra-violet detection, the polymorphisms of C677T in exon 4 of MTHFR gene and 844ins68 in exon 8 of CBS gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 105 AD patients and 102 non-AD controls. All controls were excluded from cardiocerebrovascular disorders and other diseases. Results The plasma Hcy level in AD patients (16.04 ± 3.84 μmol/L) was significantly higher than that in the controls(11.94 ± 3.87 μmol/L, P < 0.001). There were no significant differences of the genotype and allele frequencies of MTHFR C677T mutation and CBS 844ins68 mutation between the patients and controls. However, the T allele of MTHFR gene was found to relate with the plasma Hcy level increase in all subjects. Conclusion The elevated plasma Hcy level in AD patients is probably involved in the pathogenesis of AD, which may be due to the environmental factor rather than genetic factors of the mutations of MTHFR and CBS.
基金supported by grants from the National Natural Science Foundation of China(No.30850004 and No.81170402)
文摘This study aimed to observe changes in the hydrogen sulfide(H_2S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H_2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H_2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15 th, 30 th, and 52 nd day. The expression of cystathionine β-synthase(CBS) and cystathionine γ-lyase(CSE) protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction(RT-PCR), respectively. The results indicated that H_2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H_2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mR NA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H_2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H_2S protects vascular remodelling in the liver, and that CSE is indispensable in this process.
基金We thank Professor Jun-Bao Du for providing experimental suggestions and advice, and our study was supported by the National Natural Science Foundation of China (No. 30571851 to Jie Jill, No. 81201527 to Hui Guo).
文摘We investigated the expression of hydrogen sulphide (H2S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley (SD) rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine β-synthase (CBS), cystathionine y lyase (CSE) and 3-mercaptopyruvate sulphur transferase (MPST, as known as 3-MST) by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine (L-Cys, a substrate of CBS, CSE and MPST) elicited relaxation in a dose-dependent manner on human bladder strips ere-contracted by acetylcholine chloride. This effect could be diminished by the ATe-sensitive potassium ion (KATe) channel blocker glibenclamide (GLB), the CSE inhibitor DL-propargylglycine (PEG) and the CBS inhibitor hydroxylamine (HA). H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms (LUTS) or overactive bladder (OAB).
基金supported by1R01EY030054(MA),NIH-1R01EY029751(AT)supported in part by National Center for Research Resources,National Institutes of Health Grant S10RR027926.
文摘Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.