ArticleAmerican journal of physiology. Heart and circulatory physiology2015
The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Metabolic remodeling of substrate utilization during heart failure progression.Heart failure reviews · 2019Pooled it
- Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Inhibiting SHP2 improves ventricular remodeling by restoring AMPK phosphorylation and mitochondrial homeostasis.Cell communication and signaling : CCS · 2026Article
- The Role of Mitochondrial Permeability Transition in Bone Metabolism, Bone Healing, and Bone Diseases.Biomolecules · 2024Review
- Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment.International journal of molecular sciences · 2023Review
- AMPK Signalling Pathway: A Potential Strategy for the Treatment of Heart Failure with Chinese Medicine.Journal of inflammation research · 2023Review
- Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.Journal of cellular and molecular medicine · 2022Review
- Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome.International journal of molecular sciences · 2022Article
- Thymoquinone ameliorates pressure overload-induced cardiac hypertrophy by activating the AMPK signalling pathway.Journal of cellular and molecular medicine · 2022Article
- Proximal tubule cyclophilin D mediates kidney fibrogenesis in obstructive nephropathy.American journal of physiology. Renal physiology · 2021Article
- Structural and functional remodeling of mitochondria as an adaptive response to energy deprivation.Biochimica et biophysica acta. Bioenergetics · 2021Article
- Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance.Scientific reports · 2021Article
- Targeting the Mitochondrial Permeability Transition Pore to Prevent Age-Associated Cell Damage and Neurodegeneration.Oxidative medicine and cellular longevity · 2021Review
- Anomalous AMPK-regulated angiotensin ATJournal of biomedical science · 2020Article
- Autophagy-dependent and -independent modulation of oxidative and organellar stress in the diabetic heart by glucose-lowering drugs.Cardiovascular diabetology · 2020Review
- The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity.Cardiovascular drugs and therapy · 2020Review
- Proximal tubule cyclophilin D regulates fatty acid oxidation in cisplatin-induced acute kidney injury.Kidney international · 2020Article
- Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen SpeciesOxidative medicine and cellular longevity · 2019Article
- Cyclophilin D, Somehow a Master Regulator of Mitochondrial Function.Biomolecules · 2018Review
- Elucidating the contribution of ETC complexes I and II to the respirasome formation in cardiac mitochondria.Scientific reports · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
AMP kinase (AMPK) plays an important role in the regulation of energy metabolism in cardiac cells. Furthermore, activation of AMPK protects the heart from myocardial infarction and heart failure. The present study examines whether or not AMPK affects the peroxisome proliferator-activated receptor-α (PPARα)/mitochondria pathway in response to acute oxidative stress in cultured cardiomyocytes. Cultured H9c2 rat embryonic cardioblasts were exposed to H2O2-induced acute oxidative stress in the presence or absence of metformin, compound C (AMPK inhibitor), GW6471 (PPARα inhibitor), or A-769662 (AMPK activator). Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death. In addition, metformin attenuated reactive oxygen species generation and depolarization of the inner mitochondrial membrane. The antioxidative effects of metformin were associated with the prevention of mitochondrial DNA damage in cardiomyocytes. Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARα and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation. The beneficial effects of metformin were not due to acetylation or phosphorylation of PPARα in response to oxidative stress. In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARα-CypD interactions, independent of phosphorylation and acetylation of PPARα and CypD.
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