近年来研究发现1,25-二羟维生素D3（1,25-（OH）2D3）及其类似物具有独立于钙磷调节之外的许多功能,这些功能是结合细胞内维生素D受体（vitamin D receptor,VDR）后发挥作用的.而足细胞是维持肾小球功能的重要细胞,足细胞上表达VDR.因此...近年来研究发现1,25-二羟维生素D3（1,25-（OH）2D3）及其类似物具有独立于钙磷调节之外的许多功能,这些功能是结合细胞内维生素D受体（vitamin D receptor,VDR）后发挥作用的.而足细胞是维持肾小球功能的重要细胞,足细胞上表达VDR.因此1,25-（OH）2D3及其类似物与足细胞功能之间的相互关系值得探索.本文就近年来活性维生素D3及其类似物对足细胞的保护作用研究进展作一介绍.展开更多
该文研究羊肚菌蛋白水解物(morchella protein hydrolysate,MPH)及其硒化衍生物(Se-MPH)的细胞保护作用和安全性。利用H_(2)O_(2)诱导的Caco-2细胞氧化损伤模型研究了MPH和Se-MPH的细胞保护作用。结果显示,MPH和Se-MPH可通过减轻氧化应...该文研究羊肚菌蛋白水解物(morchella protein hydrolysate,MPH)及其硒化衍生物(Se-MPH)的细胞保护作用和安全性。利用H_(2)O_(2)诱导的Caco-2细胞氧化损伤模型研究了MPH和Se-MPH的细胞保护作用。结果显示,MPH和Se-MPH可通过减轻氧化应激和抑制细胞凋亡来保护Caco-2细胞免受氧化损伤,这种保护作用可能主要归因于Nrf2信号通路的激活和凋亡相关蛋白表达的调节。通过细胞毒性试验、红细胞溶血实验、细菌回复突变(bacterial reverse mutation,Ames)试验以及鸡胚绒毛尿囊膜(chick embryo chorioallantoic membrane,CAM)试验研究了MPH和Se-MPH的安全性。结果证实,MPH和Se-MPH没有细胞毒性、溶血活性和致突变潜力,在CAM实验中未观察到明显的血管形态学变化及出血现象。所有这些研究表明,MPH和Se-MPH具有显著的细胞保护作用和良好的安全性,有望作为潜在的营养性、功能性或药物性成分得到开发利用。展开更多
Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat car...Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.展开更多
Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improvi...Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglntide can perform direct protective effects on cardiomyocytes against reperfusion injury. Methods In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation （H/R） induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential （AWm） and intracellular reactive oxygen species （ROS） was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2＋ concentration and calcium transient. Immtmofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2＋-ATPase （SERCA2a）. In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. Results In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. △mψ of cardiomyocytes was higher in liraglntide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2＋ overload and improved calcium transient compared with H/R group, lmmunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Conclusions Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.展开更多
BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, M...BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, MTT assay and hoechst dye staining to check this mechanism in SKNSH and U251 cell lines. [WT5”BX]Results. Both 2mmol/L H 2O 2 and 0 5 μ mol/L amyloid β protein (Aβ) induce these two cell lines die via apoptosis. Either melatonin or glutathione can significantly protect both cell lines. The protective effect of 10 μ mol/L melatonin is as same as that of 60 μ mol/L glutathione. [WT5”BX]Conclusion. Melatonin can partly inhibit the cytotoxicity of H 2O 2 and Aβ through its role as a free radical scavenger.展开更多
Objective: To establish the rat model with myocardial hypoxia/reoxygenation (H/R) injury, and investigate the protective effect of EPO pretreatment on the myocardium. Methods: Sixty male adult Wistar rats were randoml...Objective: To establish the rat model with myocardial hypoxia/reoxygenation (H/R) injury, and investigate the protective effect of EPO pretreatment on the myocardium. Methods: Sixty male adult Wistar rats were randomly divided into 3 groups: control group, H/R group, and EPO group, 20 in each group. The rats in EPO group accepted injection of 5 000 U/kg recombinant human erythropoietin (RHuEPO) through vein, and the other rats accepted the injection of the same volume of saline. Twenty-four hours after the injection, rats in the EPO and H/R groups were put into the hypoxia environment for 12 h and then returned to the normoxic environment for 2 h, and then the samples of blood and myocardium were collected. Serum myocardial enzyme activity, apoptosis, ultrastructure, myocardial MDA contents, EPO receptor (EPOR) expression in cardiac myocytes and cardiac functions were tested. Results: EPOR expression was positive in cardiac myocytes of adult rat according to the result of immunonistochemitry assaying. Compared to those in H/R group, rats in EPO group presented lighter injury of myocardial ultrastructure, the reduction of serum myocardial enzyme activity, inhibition of apoptosis, the better recovery of cardiac functions, and the less production of oxygen-derived free radicals. Conclusion: Adult rat cardiac myocytes could express EPOR, and EPO pretreatment produced protective effects on myocardium with H/R injury.展开更多
文摘近年来研究发现1,25-二羟维生素D3（1,25-（OH）2D3）及其类似物具有独立于钙磷调节之外的许多功能,这些功能是结合细胞内维生素D受体（vitamin D receptor,VDR）后发挥作用的.而足细胞是维持肾小球功能的重要细胞,足细胞上表达VDR.因此1,25-（OH）2D3及其类似物与足细胞功能之间的相互关系值得探索.本文就近年来活性维生素D3及其类似物对足细胞的保护作用研究进展作一介绍.
基金This study was supported by the Ministry Science Foundation of the Chinese People's Liberation Army during the 12th Five-Year Plan Period
文摘Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.
基金This work is supported by grants from National Natural Science Foundation of China （No. 81102079） and China Postdoctoral Science Foundation （No. 201003776）. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors report no conflict of interest. The authors are responsible for the content and writing of the paper.
文摘Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglntide can perform direct protective effects on cardiomyocytes against reperfusion injury. Methods In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation （H/R） induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential （AWm） and intracellular reactive oxygen species （ROS） was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2＋ concentration and calcium transient. Immtmofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2＋-ATPase （SERCA2a）. In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. Results In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. △mψ of cardiomyocytes was higher in liraglntide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2＋ overload and improved calcium transient compared with H/R group, lmmunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Conclusions Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.
基金This project is supported by Korea Science & EngineeringFoundation (KOSEF) and Korea Ministry of Science &Technology
文摘BZ]To investigate the exact mechanism of melatonin to prohibit the apoptosis of neural cells induced by various kinds of cytotoxic agents. [WT5”BX]Methods. [WT5”BZ]We used the methods of phase contrast microscopy, MTT assay and hoechst dye staining to check this mechanism in SKNSH and U251 cell lines. [WT5”BX]Results. Both 2mmol/L H 2O 2 and 0 5 μ mol/L amyloid β protein (Aβ) induce these two cell lines die via apoptosis. Either melatonin or glutathione can significantly protect both cell lines. The protective effect of 10 μ mol/L melatonin is as same as that of 60 μ mol/L glutathione. [WT5”BX]Conclusion. Melatonin can partly inhibit the cytotoxicity of H 2O 2 and Aβ through its role as a free radical scavenger.
文摘Objective: To establish the rat model with myocardial hypoxia/reoxygenation (H/R) injury, and investigate the protective effect of EPO pretreatment on the myocardium. Methods: Sixty male adult Wistar rats were randomly divided into 3 groups: control group, H/R group, and EPO group, 20 in each group. The rats in EPO group accepted injection of 5 000 U/kg recombinant human erythropoietin (RHuEPO) through vein, and the other rats accepted the injection of the same volume of saline. Twenty-four hours after the injection, rats in the EPO and H/R groups were put into the hypoxia environment for 12 h and then returned to the normoxic environment for 2 h, and then the samples of blood and myocardium were collected. Serum myocardial enzyme activity, apoptosis, ultrastructure, myocardial MDA contents, EPO receptor (EPOR) expression in cardiac myocytes and cardiac functions were tested. Results: EPOR expression was positive in cardiac myocytes of adult rat according to the result of immunonistochemitry assaying. Compared to those in H/R group, rats in EPO group presented lighter injury of myocardial ultrastructure, the reduction of serum myocardial enzyme activity, inhibition of apoptosis, the better recovery of cardiac functions, and the less production of oxygen-derived free radicals. Conclusion: Adult rat cardiac myocytes could express EPOR, and EPO pretreatment produced protective effects on myocardium with H/R injury.
