Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3β and mitochondrial permeability transition pore
Open accessAbstract
Resveratrol pretreatment can protect the heart by inducing pharmacological preconditioning. Whether resveratrol protects the heart when applied at reperfusion remains unknown. We examined the effect of resveratrol on myocardial infarct size when given at reperfusion and investigated the mechanism underlying the effect. Isolated rat hearts were subjected to 30 min ischemia followed by 2 h of reperfusion, and myocardial samples were collected from the risk zone for Western blot analysis. Mitochondrial swelling was spectrophotometrically measured as a decrease in absorbance at 520 nm (A(520)). Resveratrol reduced infarct size and prevented cardiac mitochondrial swelling. Resveratrol enhanced GSK-3beta phosphorylation upon reperfusion, an effect that was mediated by the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway. Resveratrol translocated GSK-3beta from cytosol to mitochondria via the cGMP/PKG pathway. Further studies showed that mitochondrial GSK-3beta was co-immunoprecipitated with cyclophilin D but not with VDAC (voltage dependent anion channel) or ANT (adenine nucleotide translocator). These data suggest that resveratrol prevents myocardial reperfusion injury presumably by targeting the mPTP through translocation of GSK-3beta from cytosol to mitochondria. Translocated GSK-3beta may ultimately interact with cyclophilin D to modulate the mPTP opening.
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The effect of resveratrol on autophagy and mitophagy depends on inhibition of mPTP.
“and it appears that this effect also depends on the inhibition of mPTP [265,266,267,268].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [266]
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The mitochondrial permeability transition: Nexus of aging, disease and longevity
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- Authors
- Xi, J., Wang, H., Mueller, R. A., Norfleet, E. A., & Xu, Z.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Xu, Zhelong
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 604
- Issue
- 1-3
- Pages
- 111-116
- ISSN
- 0014-2999 (ISSN-L)
- PMC
- PMC2861585
- OpenAlex
- W1990435925
- Cited by
- 123
- References
- 43
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 8 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 7 · 2012: 11
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL08336, R01HL083362)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- resveratrol, cardioprotection, myocardial ischemia-reperfusion injury, glycogen synthase kinase-3β, mitochondrial permeability transition pore, cyclophilin D, mitochondrial swelling, infarct size, mitochondrial translocation, ischemia-reperfusion
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Resveratrol, Mitochondrial Permeability Transition Pore, Animals, Cardiotonic Agents, Male, Mitochondria, Heart, Mitochondrial Swelling, Myocardial Infarction, Stilbenes, Blotting, Western, Myocardial Reperfusion Injury, Rats, Wistar, Myocytes, Cardiac, Mitochondrial Membrane Transport Proteins, Glycogen Synthase Kinase 3, Immunoprecipitation, Rats, In Vitro Techniques
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