Endoplasmic reticulum stress‐mediated autophagy protects against lipopolysaccharide‐induced apoptosis in HL‐1 cardiomyocytes

作者：Xiaojing Zou, Jianjun Xu, Shanglong Yao, Jian Li, Yan Yang, Le Yang · 发表于：Experimental Physiology · 年份：2014 · DOI：10.1113/expphysiol.2014.079012 · 被引用次数：41 · 研究领域：Autophagy in Disease and Therapy、Endoplasmic Reticulum Stress and Disease、Calcium signaling and nucleotide metabolism

New Findings What is the central question of this study? Cardiac dysfunction in sepsis is associated with apoptosis of cardiomyocytes. Is endoplasmic reticulum (ER) stress induced in lipopolysaccharide (LPS)‐treated cardiomyocytes? Does ER stress‐induced autophagy protect against LPS‐induced apoptosis of cardiomyocytes? What is the mechanism in detail? What is the main finding and its importance? Our results indicate that ER stress is activated and mediates autophagy in LPS‐treated murine atrium‐derived cardiac HL‐1 cells. Protein kinase regulated by RNA‐like ER‐associated kinase (PERK), one arm of ER stress, is involved in protecting against LPS‐induced apoptosis of HL‐1 cells by promotion of autophagy. Apoptosis of cardiomyocytes limits the contractile efficiency of the heart during sepsis. Prosurvival autophagy has been proposed as a novel mechanism to maintain normal heart function. Here, we demonstrated that autophagy was activated in lipopolysaccharide (LPS)‐treated HL‐1 cells, and it counteracted the LPS‐induced apoptosis. We investigated further the mechanism by which LPS triggered autophagy in HL‐1 cells. We discovered that endoplasmic reticulum (ER) stress played an important role in LPS‐triggered autophagy. The ER activated a survival pathway through the ER‐localized transmembrane protein PERK, which was essential for LPS‐induced autophagy. Lipopolysaccharide increased expression of GRP78, phosphorylated PERK and phosphorylated eukaryotic initiation factor 2 α . Si...