GRP78 effectively protect hypoxia/reperfusion-induced myocardial apoptosis via promotion of the Nrf2/HO-1 signaling pathway
© 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC..
Myocardial infarction is a major cause of death worldwide. Despite our understanding of the pathophysiology of myocardial infarction and the therapeutic options for treatment have improved substantially, acute myocardial infarction remains a leading cause of morbidity and mortality. Recent findings revealed that GRP78 could protect myocardial cells against ischemia reperfusion injury-induced apoptosis, but the exact function and molecular mechanism remains unclear. In this study, we aimed to explore the effects of GRP78 on hypoxia/reperfusion (H/R)-induced cardiomyocyte injury. Intriguingly, we first observed that GRP78 overexpression significantly protected myocytes from H/R-induced apoptosis. On mechanism, our work revealed that GRP78 protected myocardial cells from hypoxia/reperfusion-induced apoptosis via the activation of the Nrf2/HO-1 signaling pathway. We observed the enhanced expression of Nrf2/HO-1 in GRP78 overexpressed H9c2 cell, while GRP78 deficiency dramatically antagonized the expression of Nrf2/HO-1. Furthermore, we found that blocked the Nrf2/HO-1 signaling by the HO-1 inhibitor zinc protoporphyrin IX (Znpp) significantly retrieved H9c2 cells apoptosis that inhibited by GRP78 overexpression. Taken together, our findings revealed a new mechanism by which GRP78 alleviated H/R-induced cardiomyocyte apoptosis in H9c2 cells via the promotion of the Nrf2/HO-1 signaling pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:236 |
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| Enthalten in: |
Journal of cellular physiology - 236(2021), 2 vom: 15. Feb., Seite 1228-1236 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ji, Heyu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.09.2021 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jcp.29929 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312341288 |
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| 245 | 1 | 0 | |a GRP78 effectively protect hypoxia/reperfusion-induced myocardial apoptosis via promotion of the Nrf2/HO-1 signaling pathway |
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| 520 | |a © 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC. | ||
| 520 | |a Myocardial infarction is a major cause of death worldwide. Despite our understanding of the pathophysiology of myocardial infarction and the therapeutic options for treatment have improved substantially, acute myocardial infarction remains a leading cause of morbidity and mortality. Recent findings revealed that GRP78 could protect myocardial cells against ischemia reperfusion injury-induced apoptosis, but the exact function and molecular mechanism remains unclear. In this study, we aimed to explore the effects of GRP78 on hypoxia/reperfusion (H/R)-induced cardiomyocyte injury. Intriguingly, we first observed that GRP78 overexpression significantly protected myocytes from H/R-induced apoptosis. On mechanism, our work revealed that GRP78 protected myocardial cells from hypoxia/reperfusion-induced apoptosis via the activation of the Nrf2/HO-1 signaling pathway. We observed the enhanced expression of Nrf2/HO-1 in GRP78 overexpressed H9c2 cell, while GRP78 deficiency dramatically antagonized the expression of Nrf2/HO-1. Furthermore, we found that blocked the Nrf2/HO-1 signaling by the HO-1 inhibitor zinc protoporphyrin IX (Znpp) significantly retrieved H9c2 cells apoptosis that inhibited by GRP78 overexpression. Taken together, our findings revealed a new mechanism by which GRP78 alleviated H/R-induced cardiomyocyte apoptosis in H9c2 cells via the promotion of the Nrf2/HO-1 signaling pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a GRP78 | |
| 650 | 4 | |a HO-1 | |
| 650 | 4 | |a Nrf2 | |
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| 650 | 4 | |a myocardial hypoxia/reperfusion | |
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| 700 | 1 | |a Xiao, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Suobei |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Ruan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Junmei |e verfasserin |4 aut | |
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