Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis

Frontiers in Physiology

Kun-Ruey Shieh²  Kun-Ta Yang²  Pei-Ching Ting³  Huai-Ren Chang⁴  Wen-Sen Lee⁵  Tsung-I Chen⁶  Wei-Fen Hu⁷  Jian-Hong Lin⁸  Jui-Chih Chang⁹ 

[1] Center for Physical Education, College of Education and Communication, Tzu Chi University, Hualien, Taiwan;Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan;Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan;Division of Cardiology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan;Graduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Institute of Education, College of Education and Communication, Tzu Chi University, Hualien, Taiwan;Master Program in Medical Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan;PhD Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan;School of Medicine, Tzu Chi University, Hualien, Taiwan;

关键词: apoptosis;    autophagy;    cell death;    endoplasmic reticulum;    intermittent hypoxia;    stress;   

DOI  :  10.3389/fphys.2019.00995

来源: DOAJ

【 摘 要 】

Intermittent hypoxia (IH), characterized as cyclic episodes of short-period hypoxia followed by normoxia, occurs in many physiological and pathophysiological conditions such as pregnancy, athlete, obstructive sleep apnea, and asthma. Hypoxia can induce autophagy, which is activated in response to protein aggregates, in the proteotoxic forms of cardiac diseases. Previous studies suggested that autophagy can protect cells by avoiding accumulation of misfolded proteins, which can be generated in response to ischemia/reperfusion (I/R) injury. The objective of the present study was to determine whether IH-induced autophagy can attenuate endoplasmic reticulum (ER) stress and cell death. In this study, H9c2 cell line, rat primary cultured cardiomyocytes, and C57BL/6 male mice underwent IH with an oscillating O2 concentration between 4 and 20% every 30 min for 1–4 days in an incubator. The levels of LC3, an autophagy indicator protein and CHOP and GRP78 (ER stress-related proteins) were measured by Western blotting analyses. Our data demonstrated that the autophagy-related proteins were upregulated in days 1–3, while the ER stress-related proteins were downregulated on the second day after IH. Treatment with H2O2 (100 μM) for 24 h caused ER stress and increased the level of ER stress-related proteins, and these effects were abolished by pre-treatment with IH condition. In response to the autophagy inhibitor, the level of ER stress-related proteins was upregulated again. Taken together, our data suggested that IH could increase myocardial autophagy as an adaptive response to prevent the ER stress and apoptosis.

【 授权许可】

Unknown