Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis
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 pr...
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00995/full |
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| author | Jui-Chih Chang Jui-Chih Chang Wei-Fen Hu Wen-Sen Lee Jian-Hong Lin Pei-Ching Ting Huai-Ren Chang Huai-Ren Chang Kun-Ruey Shieh Kun-Ruey Shieh Kun-Ruey Shieh Tsung-I Chen Tsung-I Chen Kun-Ta Yang Kun-Ta Yang |
| author_facet | Jui-Chih Chang Jui-Chih Chang Wei-Fen Hu Wen-Sen Lee Jian-Hong Lin Pei-Ching Ting Huai-Ren Chang Huai-Ren Chang Kun-Ruey Shieh Kun-Ruey Shieh Kun-Ruey Shieh Tsung-I Chen Tsung-I Chen Kun-Ta Yang Kun-Ta Yang |
| author_sort | Jui-Chih Chang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T08:40:06Z |
| format | Article |
| id | doaj.art-a9096fd819a74c448be7364f46b312a3 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T08:40:06Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-a9096fd819a74c448be7364f46b312a32022-12-22T01:55:52ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-08-011010.3389/fphys.2019.00995469425Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and ApoptosisJui-Chih Chang0Jui-Chih Chang1Wei-Fen Hu2Wen-Sen Lee3Jian-Hong Lin4Pei-Ching Ting5Huai-Ren Chang6Huai-Ren Chang7Kun-Ruey Shieh8Kun-Ruey Shieh9Kun-Ruey Shieh10Tsung-I Chen11Tsung-I Chen12Kun-Ta Yang13Kun-Ta Yang14Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, TaiwanSchool of Medicine, Tzu Chi University, Hualien, TaiwanMaster Program in Medical Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanGraduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanPhD Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, TaiwanDepartment of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, TaiwanSchool of Medicine, Tzu Chi University, Hualien, TaiwanDivision of Cardiology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, TaiwanSchool of Medicine, Tzu Chi University, Hualien, TaiwanMaster Program in Medical Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanDepartment of Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanCenter for Physical Education, College of Education and Communication, Tzu Chi University, Hualien, TaiwanInstitute of Education, College of Education and Communication, Tzu Chi University, Hualien, TaiwanMaster Program in Medical Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanDepartment of Physiology, School of Medicine, Tzu Chi University, Hualien, TaiwanIntermittent 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.https://www.frontiersin.org/article/10.3389/fphys.2019.00995/fullapoptosisautophagycell deathendoplasmic reticulumintermittent hypoxiastress |
| spellingShingle | Jui-Chih Chang Jui-Chih Chang Wei-Fen Hu Wen-Sen Lee Jian-Hong Lin Pei-Ching Ting Huai-Ren Chang Huai-Ren Chang Kun-Ruey Shieh Kun-Ruey Shieh Kun-Ruey Shieh Tsung-I Chen Tsung-I Chen Kun-Ta Yang Kun-Ta Yang Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis Frontiers in Physiology apoptosis autophagy cell death endoplasmic reticulum intermittent hypoxia stress |
| title | Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis |
| title_full | Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis |
| title_fullStr | Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis |
| title_full_unstemmed | Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis |
| title_short | Intermittent Hypoxia Induces Autophagy to Protect Cardiomyocytes From Endoplasmic Reticulum Stress and Apoptosis |
| title_sort | intermittent hypoxia induces autophagy to protect cardiomyocytes from endoplasmic reticulum stress and apoptosis |
| topic | apoptosis autophagy cell death endoplasmic reticulum intermittent hypoxia stress |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00995/full |
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