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Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury.
- Source :
-
In vitro cellular & developmental biology. Animal [In Vitro Cell Dev Biol Anim] 2016 Jun; Vol. 52 (6), pp. 690-8. Date of Electronic Publication: 2016 Apr 29. - Publication Year :
- 2016
-
Abstract
- Irreversible damage of cardiac function arisen from myocardial ischemia/reperfusion injury (MIRI) leads to an emerging challenge in the treatments of cardiac ischemic diseases. Molecular chaperone heat shock protein 70 (HSP70) attenuates heat-stimulated cell autophagy, apoptosis, and damage in the heart. Under specific conditions, autophagy may, directly or indirectly, induce cell death including necroptosis. Whether HSP70 inhibits cardiomyocyte necroptosis via suppressing autophagy during MIRI is unknown. In our study, HSP70 expression was opposite to necroptosis marker RIP1 and autophagy marker LC3A/B expression after myocardial ischemia/reperfusion (MIR) in vivo. Furthermore, in vitro primary rat cardiomyocytes mimicked MIRI by hypoxia/reoxygenation (H/R) treatment. Knockdown of HSP70 expression promoted cardiomyocyte autophagy and necroptosis following H/R treatment, while the increase tendency was downregulated by autophagy inhibitor 3-MA, showing that autophagy-induced necroptosis could be suppressed by HSP70. In summary, HSP70 downregulates cardiomyocyte necroptosis through suppressing autophagy during myocardial IR, revealing the novel protective mechanism of HSP70 and supplying a novel molecular target for the treatment of heart ischemic diseases.
- Subjects :
- Animals
Autophagy physiology
Cell Hypoxia
Down-Regulation
Gene Knockdown Techniques
HSP70 Heat-Shock Proteins antagonists & inhibitors
HSP70 Heat-Shock Proteins genetics
Immunohistochemistry
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Myocytes, Cardiac metabolism
Necrosis physiopathology
Protein Serine-Threonine Kinases
Rats
Rats, Sprague-Dawley
Receptor-Interacting Protein Serine-Threonine Kinases
HSP70 Heat-Shock Proteins physiology
Myocardial Reperfusion Injury pathology
Myocytes, Cardiac pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1543-706X
- Volume :
- 52
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- In vitro cellular & developmental biology. Animal
- Publication Type :
- Academic Journal
- Accession number :
- 27130675
- Full Text :
- https://doi.org/10.1007/s11626-016-0039-8