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首页> 外文期刊>Journal of Cellular Physiology >Acute ethanol exposure‐induced autophagy‐mediated cardiac injury via activation of the ROS‐JNK‐Bcl‐2 pathway
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Acute ethanol exposure‐induced autophagy‐mediated cardiac injury via activation of the ROS‐JNK‐Bcl‐2 pathway

机译:急性乙醇暴露量诱导自噬的调节通过激活的心脏损伤活性氧检测物检测Bcl 2通路

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摘要

Binge drinking is associated with increased cardiac autophagy, and often triggers heart injury. Given the essential role of autophagy in various cardiac diseases, this study was designed to investigate the role of autophagy in ethanol‐induced cardiac injury and the underlying mechanism. Our study showed that ethanol exposure enhanced the levels of LC3‐II and LC3‐II positive puncta and promoted cardiomyocyte apoptosis in vivo and in vitro. In addition, we found that ethanol induced autophagy and cardiac injury largely via the sequential triggering of reactive oxygen species (ROS) accumulation, activation of c‐Jun NH2‐terminal kinase (JNK), phosphorylation of Bcl‐2, and dissociation of the Beclin 1/Bcl‐2 complex. By contrast, inhibition of ethanol‐induced autophagic flux with pharmacologic agents in the hearts of mice and cultured cells significantly alleviated ethanol‐induced cardiomyocyte apoptosis and heart injury. Elimination of ROS with the antioxidant N‐acetyl cysteine (NAC) or inhibition of JNK with the JNK inhibitor SP600125 reduced ethanol‐induced autophagy and subsequent autophagy‐mediated apoptosis. Moreover, metallothionein (MT), which can scavenge reactive oxygen and nitrogen species, also attenuated ethanol‐induced autophagy and cell apoptosis in MT‐TG mice. In conclusion, our findings suggest that acute ethanol exposure induced autophagy‐mediated heart toxicity and injury mainly through the ROS‐JNK‐Bcl‐2 signaling pathway.
机译:酗酒与增加有关心脏自噬,经常引发心脏受伤。各种心脏疾病,本研究设计调查中自噬的作用乙醇诱导心肌损伤和底层机制。增强LC3的水平II和LC3 II积极puncta,促进心肌细胞凋亡体内和体外。乙醇诱导自噬和心脏损伤主要通过连续触发的反应氧物种(ROS)积累,激活的c‐焦耳NH2‐terminal kinase (JNK), phosphorylation地理的Bcl 2,离解的Beclin 1 / Bcl 2复杂。乙醇诱导自噬流量与药物在小鼠和的心培养细胞明显缓解乙醇诱导心肌细胞凋亡和心脏受伤。N乙酰半胱氨酸(NAC)或应承担的抑制物物抑制剂SP600125减少乙醇诱导自噬和随后的自噬的介导细胞凋亡。金属硫蛋白(MT),它可以清除活性氧和氮物种,也减毒乙醇诱导自噬与细胞凋亡太TG应承担的老鼠。急性乙醇暴露诱导自噬的介导心脏毒性和伤害主要通过活性氧检测物检测Bcl 2信号途径。

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