Abstract
Resveratrol is widely known for its antiaging properties and exerts cardiovascular protective effects in different experimental models. The role of resveratrol in regulating mitochondrial functions and dynamics during the cardiac aging process remains poorly understood. In this study, the effects of resveratrol on mitochondrial morphology and mitochondrial depolarization and on expressions of Drp1, parkin, PINK1, and LC3 were investigated in H9c2 cells after D-galactose treatment that induced senescent-like cardiomyocytes. The results show that downregulation of Drp1 markedly increased mitochondrial elongation. Senescent-like cardiomyocytes were more resistant to CCCP-induced mitochondrial depolarization, which was accompanied by suppressed expression of parkin, PINK1, and LC3-II. Resveratrol treatment significantly increased Drp1 expression, ameliorated mitochondrial elongation, and increased the mitochondrial translocations of parkin and PINK1. In addition, resveratrol significantly enhanced LC3-II expression and decreased TOM20-labeled mitochondrial content. Resveratrol also suppressed the phosphorylation of parkin and PINK1, which may relate to its abilities to degrade the impaired mitochondria in senescent-like cardiomyocytes. These findings show that suppressing mitochondrial elongation in a Drp1-dependent manner is involved in the effect of resveratrol on attenuating the development of aging cardiomyocytes. Activation of parkin and PINK1 may be a potential mechanism of resveratrol for treating cardiovascular complications related to aging.
Highlights
Age-related loss or attenuation of myocardial ischemic preconditioning (IPC) has been studied in animals and humans [1, 2]
We examined the morphology of mitochondria in H9c2 cells exposed to D-galactose for 48 hours (Figure 1(a))
We evaluated fission- or fusion-regulated protein (Mfn1, mitofusin 2 (Mfn2), OPA1, and dynamin-related protein-1 (Drp1)) expressions, finding that Drp1 was obviously downregulated after D-galactose induction (Figure 1(b))
Summary
Age-related loss or attenuation of myocardial ischemic preconditioning (IPC) has been studied in animals and humans [1, 2]. The dysfunctional IPC mechanisms underlying the aging process remain unclear, there is considerable agreement that mitochondria play a key role in the aging process and that specific defects in mitochondrial function are associated with age-related decline in cardiac efficiency. The role of mitochondrial dynamics focusing on organelle fission and fusion has been studied in normal and diseased hearts, and the dysfunction of mitochondrial fission and fusion was well implicated in cardiac death or disease with aging [7,8,9]. The tolerance conferred by IPC in aged cardiomyocytes is probably dependent on their ability to maintain mitochondrial dynamism, such as fusion, fission, biogenesis, and selective degradation.
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