Resveratrol promotes autophagosome elimination via SIRT1 in cardiomyocytes.

Autor:	Kuno A; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: kuno@sapmed.ac.jp., Hosoda R; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan., Saga Y; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan., Iwahara N; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan., Tatekoshi Y; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan., Numazawa R; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan., Horio Y; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Jazyk:	angličtina
Zdroj:	Journal of pharmacological sciences [J Pharmacol Sci] 2025 Jan; Vol. 157 (1), pp. 25-34. Date of Electronic Publication: 2024 Nov 28.
DOI:	10.1016/j.jphs.2024.11.006
Abstrakt:	The processes of autophagy, including autophagosome formation, fusion of autophagosomes with lysosomes, and degradation of autophagosomes by lysosomes, are regulated by various mechanisms. We recently found that treatment with resveratrol, an activator of the NAD + -dependent protein deacetylase Sirtuin-1 (SIRT1), in a mouse model prevented autophagosome accumulation in the heart with high mTORC1 activity. In this study, we investigated whether SIRT1 mediates the effects of resveratrol on autophagosome elimination using a cardiomyocyte model. In H9c2 cardiomyocytes, treatment with the mTORC1 activator MHY1485 induced autophagosome accumulation accompanied by increases in fragmented mitochondria within the autophagosomes and levels of intracellular reactive oxygen species (ROS), indicative of impaired autophagy-mediated elimination of mitochondria and resultant oxidative stress. MHY1485 suppressed the fusion of autophagosomes with lysosomes. Co-treatment with resveratrol attenuated the MHY1485-induced increases in autophagosomes, mitochondria within autophagosomes, and levels of ROS. Knockdown of Sirt1 reversed the reductions in autophagosomes and ROS levels induced by resveratrol under the condition of MHY1485 treatment. Neither resveratrol treatment nor Sirt1 knockdown modulated the phosphorylation levels of UVRAG, a target of mTORC1 for suppression of autophagosome-lysosome fusion. Our findings suggest that SIRT1 mediates the resveratrol-induced promotion of autophagosome elimination in cells with high mTORC1 activity. Competing Interests: Conflict of interest The authors indicated no potential conflict of interest. (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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