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首页> 外文期刊>Journal of Cellular Physiology >A novel adipocytokine visfatin protects against H2O2-induced myocardial apoptosis: A missing link between obesity and cardiovascular disease
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A novel adipocytokine visfatin protects against H2O2-induced myocardial apoptosis: A missing link between obesity and cardiovascular disease

机译:小说adipocytokine visfatin预防H2O2-induced心肌细胞凋亡:一个缺失的环节肥胖和心血管疾病之间的关系

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Fat accumulation in obese individuals worsens the clinical outcomes of cardiovascular disease (CVD). Paradoxically, increased circulating adipocytokines secreted from visceral fat may confer cardioprotective effects. Visfatin, a novel adipocytokine, has anti-diabetic, anti-tumor, and pro-inflammatory properties. However, its effects on cardiomyocytes and the underlying mechanisms remain unknown. This article demonstrated that visfatin counteracted H2O2-induced apoptotic damage in H9c2 cardiomyocytes in a time-dependent manner. Qualitative immunofluorescence approaches demonstrated that visfatin pretreatment attenuated H2O2-induced DNA fragmentation (TdT-mediated dUTP-biotin nick end-labeling), phosphatidyl serine exposure (Annexin V/PI staining), and mitochondrial membrane potential (ΔΨm) depolarization (JC-1 staining). Biochemical studies on cardiomyoctes showed improved cell viability and reduced caspase-3 activation caused by visfatin pretreatment. Visfatin did not inhibit the death receptor-dependent apoptotic pathways, as characterized by its absence in both Fas and TNFR1 down-regulation. Instead, visfatin specifically suppressed the mitochondria-dependent apoptotic pathways, as characterized by changed levels of p53 and its downstream Bcl-2 family genes. Visfatin also up-regulated the protein levels of phosphorylated AMPK, and the anti-apoptotic action of visfatin was attenuated by the AMPK-specific inhibitor compound C. These results suggested that visfatin plays a critical role in cardioprotection by suppressing myocardial apoptosis via AMPK activation. These findings may be the missing link between obesity and CVD.
机译:脂肪堆积在肥胖个体加剧了心血管疾病的临床结果(CVD)。从内脏脂肪可能adipocytokines分泌授予心血管效应。小说adipocytokine抗糖尿病,抗肿瘤、炎性属性。然而,它对心肌细胞的影响潜在机制仍然未知。文章证明了visfatin中和在H9c2 H2O2-induced凋亡损伤心肌细胞在时间的方式。定性的免疫荧光方法证明visfatin预处理减毒H2O2-induced DNA碎片(TdT-mediated dUTP-biotin尼克末端标记),磷脂酰丝氨酸暴露(膜联蛋白V /π染色),线粒体膜电位(ΔΨm)去极化(JC-1染色)。研究cardiomyoctes显示改进的细胞生存能力和减少caspase-3激活引起的visfatin预处理。抑制死亡receptor-dependent凋亡途径,以其在这两方面都没有Fas和TNFR1下调。特别压抑mitochondria-dependent凋亡通路以改变的p53和水平下游bcl - 2基因家族。差异蛋白质的磷酸化水平AMPK, visfatin的抗凋亡作用减毒的AMPK-specific抑制剂复合c。这些结果表明visfatin在心脏保护中起着至关重要的作用通过AMPK抑制心肌细胞凋亡激活。肥胖和心血管疾病之间的联系。

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