Zn2+ and mPTP mediate resveratrol-induced myocardial protection from endoplasmic reticulum stress
Abstract
Resveratrol displays cardioprotective activity; however, its mechanism of action remains unclear. In the current study, resveratrol-induced myocardial protection from endoplasmic reticulum stress (ERS) was investigated, focusing on the roles of Zn2+ and the mitochondrial permeability transition pore (mPTP). We found, using the MTT/LDH kit, that 2-DG-induced ERS significantly decreased H9c2 cell viability. Resveratrol markedly inhibited the expression of endoplasmic reticulum chaperone GRP 78/94 and ERS-related apoptosis proteins CHOP, Caspase12, and JNK induced by 2-DG. The zinc ion chelator TPEN, and ERK/GSK-3β inhibitors PD98059 and SB216763 and their siRNAs blocked resveratrol function. The AKT inhibitor LY294002 and siRNA did not alter the action of resveratrol. In addition, resveratrol significantly increased the phosphorylation of ERK and GSK-3β. Resveratrol prevented 2-DG-induced mPTP opening and increased intracellular Zn2+ concentration indicated by TMRE and Newport Green DCF fluorescence intensity, which were further abrogated by ERK/GSK-3β inhibitors and siRNAs. Our data suggested that resveratrol protected cardiac cells from ERS by mobilizing intracellular Zn2+ and preventing mPTP opening through the ERK/GSK-3β but not PI3K/AKT signaling pathway.
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Protection from ER stress by resveratrol depends on inhibition of mPTP.
“Similarly, protection from ER stress by resveratrol depends on the inhibition of mPTP [269].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [269]
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- Authors
- He, Y., Fu, Y., Xi, M., Zheng, H., Zhang, Y., Liu, Y., Zhao, Y., Xi, J., & He, Y.
- Affiliations
- North China University of Science and Technology (CN)
- Dalian Medical University (CN)
- Corresponding author
- Xi, Jinkun
- He, Yonggui
- Venue
- Metallomics
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12-10
- Volume
- 12
- Issue
- 2
- Pages
- 290-300
- ISSN
- 1756-5901 (ISSN-L)
- 1756-591X
- OpenAlex
- W2995500171
- Cited by
- 31
- References
- 56
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Metallomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81570275)
- Natural Science Foundation of Hebei Province (H2018209309)
- Department of Education of Hebei Province (SLRC2017051)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- resveratrol, endoplasmic reticulum stress, zinc ions, mitochondrial permeability transition pore, cardioprotection, CHOP, JNK, 2-deoxyglucose, H9c2 cells, TPEN, ERK inhibitor, GSK-3β inhibitors
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Resveratrol, Mitochondrial Permeability Transition Pore, Animals, Cardiotonic Agents, Cell Line, Chromones, Morpholines, Zinc, Signal Transduction, Myocytes, Cardiac, Rats, Endoplasmic Reticulum Stress
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