科研之友
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摘要
Context and objectives: Advanced glycation end products (AGEs) can induce scnescence in cardiomyocytes. However, its underlying molecular mechanisms remain unknown. Methods: Neonatal rat cardiomyocytes were incubated with AGEs, and cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) activity and aging-associated p16 expression. In addition, mitophagic activity was evaluated by measuring the expression of the PINK1, Parkin, LC3 and p62 proteins. The mitophagy inhibitor cyclosporine A (CsA) or PINK1 siRNAs was then administered to cardiomyocytes to study the role of mitophagy in AGE-induced aging. Results: A significantly increased number of SA-beta-gal positive cells and increased p16 protein levels were observed in cardiomyocytes treated with AGES. Moreover, AGES significantly increased the protein levels of PINK] and Parkin as well as the LC3-II/LC3-1 ratio, which occurred in a dose-dependent manner. However, the expression of p62 decreased significantly in the AGE group compared to the control. Surprisingly, both CsA and the knockdown of PINK] by small-interfeli lig RNA (siRNA) significantly decreased the LC3-II/LC3-1 ratio and the PINK1 and Parkin protein levels in AGE-treated cardiomyocytes, Moreover, CsA treatment or knockdown of PINK] expression attenuated the increased number of SA-beta-gal positive cells and the upregulated p16 level in cardiomyocytes induced by AGEs. Conclusions: PINK1/Parkin-mecliaecl mitophagy is involved in the process of carcliomymyle senescence induced by AGEs, and a reduction in mitophagic activity might be a promising approach Lo block the senescent state in cardiomymy Les.
- 出版日期2017-1-15
- 单位南京医科大学
