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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

The Newly Proposed Mechanism of Cardiomyocyte Protection of Carvedilol- Anti-Apoptosis Pattern of Carvedilol in Anoxia by Inducing Autophagy Partly through the AMPK/mTOR Pathway

Author(s): Jingru Li, Chaozhong Li, Guihu Sun, Longjun Li, Yongli Zeng, Huawei Wang, Xinyu Wu, Ping Yang, Yunzhu Peng* and Luqiao Wang*

Volume 20, Issue 10, 2023

Published on: 18 August, 2022

Page: [1600 - 1609] Pages: 10

DOI: 10.2174/1570180819666220513150100

Price: $65

Abstract

Purpose: To investigate the underlying mechanism of cardiomyocyte protection of carvedilol based on autophagy and apoptosis.

Methods: Neonatal rat ventricular myocytes (NRVMs) were exposed to various concentrations of carvedilol before anoxia, and pretreated with 3-MA or compound C for inhibiting autophagy or p-AMPK expression. CCK-8 colorimeter and flow cytometry were used to determine the cell viability and apoptotic rates. The variation of mRNA and protein was measured by RT-PCR and Western blot. The presence of autophagosomes was observed by electron microscopy.

Results: First, we found that carvedilol increased autophagic marker levels in a concentration-dependent manner and the number of autophagosomes in NRVMs. Moreover, carvedilol substantially enhanced the viability and noticeably reduced the CK, MDA and LDH levels and cell apoptosis rate compared with the anoxia group. In addition, carvedilol decreased the levels of caspase-3 and Bim in mRNA and protein, but such effect was blocked by the special autophagy inhibitor-3-MA, and the number of autophagosomes was significantly decreased when treated with 3-MA, indicating that carvedilol exhibited anti-apoptotic and anti-injury effects by inducing autophagy in anoxia NRVMs, but these effects can be abolished by adding 3-MA to suppress autophagy. Finally, the carvedilol treatment-induced autophagy by enhancing the activation of p-AMPK and inhibiting p-mTOR. Electron microscopy presented that the number of autophagosomes was significantly decreased when treating with compound C, indicating that carvedilol induced autophagy in anoxia NRVMs partly by the AMPK-mTOR signaling pathway.

Conclusion: Carvedilol has cardioprotection by inducing autophagy against apoptosis partly through the AMPK/mTOR pathway during anoxia in NRVMs.

Keywords: Carvedilol, autophagy, anoxia, apoptosis, AMPK/mTOR signal pathway, cardiomyocyte protection.

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