Adiponectin inhibits D‑gal‑induced cardiomyocyte senescence via AdipoR1/APPL1

Liu,Ruiying; Meng,Jing; Lou,Danfei

doi:10.3892/mmr.2021.12358

Adiponectin inhibits D‑gal‑induced cardiomyocyte senescence via AdipoR1/APPL1

Authors:
- Ruiying Liu
- Jing Meng
- Danfei Lou
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Affiliations: Department of Geriatric Cardiovascular, General Hospital of Southern Theater Command, Chinese People's Liberation Army, Guangzhou, Guangdong 510010, P.R. China, Department of Geriatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China, Department of Geriatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, P.R. China
Published online on: August 10, 2021 https://doi.org/10.3892/mmr.2021.12358
Article Number: 719
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to examine whether adiponectin could inhibit cardiomyocyte senescence induced by D‑galactose (D‑gal), and whether it functioned via the adiponectin receptor 1 (AdipoR1)/adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) signaling pathway. For this purpose, the expression levels of adiponectin, AdipoR1 and APPL1 in mouse plasma and myocardial tissues were detected via reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. An adiponectin‑overexpression plasmid was transfected into D‑gal‑treated H9c2 cells prior to the detection of AdipoR1 and APPL1 expression by RT‑qPCR. Senescence‑associated β‑galactose staining was then performed to observe cellular senescence following the transfection of small interfering RNAs (si) targeting AdipoR1 and APPL1 into D‑gal‑treated H9c2 cells overexpressing adiponectin. Commercial kits were used to detect reactive oxygen species (ROS) production and malondialdehyde (MDA) content in the different groups. The expression levels of heme oxygenase (HO)‑1 and high mobility group box 1 (HMGB1) were examined by western blot analysis. The results revealed that the expression levels of adiponectin, AdipoR1 and APPL1 were downregulated in aged mouse plasma, myocardial tissues and D‑gal‑treated cardiomyocytes. It was also observed that AdipoR1 and APPL1 expression levels were significantly upregulated following the overexpression of adiponectin into D‑gal‑treated cardiomyocytes. Moreover, adiponectin overexpression reduced cellular senescence induced by D‑gal and the expression of p16 and p21; these effects were reversed following transfection with si‑AdipoR1 and si‑APPL1. Adiponectin also downregulated the levels of ROS and MDA in D‑gal‑treated H9c2 cells via AdipoR1/APPL1. Additionally, the release of HO‑11/HMGB1 was affected by adiponectin via AdipoR1/APPL1, and adiponectin/AdipoR1/APPL1 suppressed ROS production via HO‑1/HMGB1. On the whole, the present study demonstrated that adiponectin played an inhibitory role in cardiomyocyte senescence via the AdioR1/APPL1 signaling pathway and inhibited the levels of oxidative stress in senescent cardiomyocytes via the HO‑1/HMGB1 signaling pathway.

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