Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed wi...Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency.However,whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.Methods：Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment.The contents of lactate dehydrogenase （LDH）,superoxide dismutase （SOD）,and malondialdehyde （MDA） in H9c2 cells were measured to investigate oxidative stress levels.The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry.The expression levels of proteins in the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （AKT）/P53 signaling pathway,inducible NOS （iNOS）,and endothelial NOS （eNOS） were examined using Western blotting.Results：X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner,whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition （control group vs.X-ray groups,respectively,P 〈 0.0 l）.X-ray radiation induced LDH release,apoptosis,and G0/G 1 peak accumulation,significantly increasing the level of MDA and the production of NO,and decreased the level of SOD （control group vs.X-ray groups,respectively,P 〈 0.05 or P 〈 0.01）.By contrast,BH4 treatment can significantly reverse these processes （BH4 treatment groups vs.X-ray groups,P 〈 0.05 or P 〈 0.01）.BH4 reversed the X-ray radiation-induced expression alterations ofapoptosis-related molecules,including B-cell lymphoma-2 （Bcl-2）,Bcl-2 associated X protein,and caspase-3,and molecules of the PI3K/Akt/P53 signaling pathway.BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.Conclusions：BH4 treatment can protect against X-ray-induced cardiomyocyte injury,possibly by recoupling eNOS rather than iNOS.BH4 treatment also decreased oxidative stress in radiated H9c2 cells.展开更多
Objective To investigate the effect and mechanism of tetrahydrobiopterin(BH4)on the angiogenesis in hepatocellular carcinoma(HCC).Methods BALB/c-nu mice were subcutaneously injected with Hep G-2 cells and randomly div...Objective To investigate the effect and mechanism of tetrahydrobiopterin(BH4)on the angiogenesis in hepatocellular carcinoma(HCC).Methods BALB/c-nu mice were subcutaneously injected with Hep G-2 cells and randomly divided into control and BH4 groups.The展开更多
Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control...Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.展开更多
基金This work was supported by the National Natural Science Foundation of China （No. 81270332）, and Gansu Province Health Industry Scientific Research Plan （No. GSWSKY-2014-33）.
文摘Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency.However,whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.Methods：Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment.The contents of lactate dehydrogenase （LDH）,superoxide dismutase （SOD）,and malondialdehyde （MDA） in H9c2 cells were measured to investigate oxidative stress levels.The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry.The expression levels of proteins in the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （AKT）/P53 signaling pathway,inducible NOS （iNOS）,and endothelial NOS （eNOS） were examined using Western blotting.Results：X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner,whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition （control group vs.X-ray groups,respectively,P 〈 0.0 l）.X-ray radiation induced LDH release,apoptosis,and G0/G 1 peak accumulation,significantly increasing the level of MDA and the production of NO,and decreased the level of SOD （control group vs.X-ray groups,respectively,P 〈 0.05 or P 〈 0.01）.By contrast,BH4 treatment can significantly reverse these processes （BH4 treatment groups vs.X-ray groups,P 〈 0.05 or P 〈 0.01）.BH4 reversed the X-ray radiation-induced expression alterations ofapoptosis-related molecules,including B-cell lymphoma-2 （Bcl-2）,Bcl-2 associated X protein,and caspase-3,and molecules of the PI3K/Akt/P53 signaling pathway.BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.Conclusions：BH4 treatment can protect against X-ray-induced cardiomyocyte injury,possibly by recoupling eNOS rather than iNOS.BH4 treatment also decreased oxidative stress in radiated H9c2 cells.
文摘Objective To investigate the effect and mechanism of tetrahydrobiopterin(BH4)on the angiogenesis in hepatocellular carcinoma(HCC).Methods BALB/c-nu mice were subcutaneously injected with Hep G-2 cells and randomly divided into control and BH4 groups.The
基金funded by the Universiti Tunku Abdul Rahman Research fund(IPSR/RMC/UTARRF/2019-C2/L08)。
文摘Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.
