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Adiponectin up-regulates the decrease of myocardial autophagic flux induced by β 1 -adrenergic receptor autoantibody partly dependent on AMPK.

Authors :
Sun C
Lu J
Long Y
Guo S
Jia W
Ning N
Hao H
Wang X
Bian Y
Liu H
Wang L
Source :
Journal of cellular and molecular medicine [J Cell Mol Med] 2021 Sep; Vol. 25 (17), pp. 8464-8478. Date of Electronic Publication: 2021 Jul 29.
Publication Year :
2021

Abstract

Cardiomyocytes autophagy is essential for maintaining cardiac function. Our previous studies have found that β <subscript>1</subscript> -adrenergic receptor autoantibody (β <subscript>1</subscript> -AA) induced the decreased myocardial autophagic flux, which resulted in cardiomyocyte death and cardiac dysfunction. And other studies demonstrated that β <subscript>1</subscript> -AA induced the decrease of AMPK phosphorylation, the key hub of autophagy pathway, while adiponectin up-regulated autophagic flux mediated by AMPK. However, it is not clear whether adiponectin improves the inhibition of myocardial autophagic flux induced by β <subscript>1</subscript> -AA by up-regulating the level of AMPK phosphorylation. In this study, it has been confirmed that β <subscript>1</subscript> -AA induced the decrease of AMPK phosphorylation level in both vivo and vitro. Moreover, pretreatment of cardiomyocytes with AMPK inhibitor Compound C could further reduce the autophagic flux induced by β <subscript>1</subscript> -AA. Adiponectin deficiency could aggravate the decrease of myocardial AMPK phosphorylation level, autophagic flux and cardiac function induced by β <subscript>1</subscript> -AA. Further, exogenous adiponectin could reverse the decline of AMPK phosphorylation level and autophagic flux induced by β <subscript>1</subscript> -AA and even reduce cardiomyocyte death. While pretreated with the Compound C, the adiponectin treatment did not improve the decreased autophagosome formation, but still improved the decreased autophagosome clearance induced by β <subscript>1</subscript> -AA in cardiomyocytes. This study is the first time to confirm that β <subscript>1</subscript> -AA could inhibit myocardial autophagic flux by down-regulating AMPK phosphorylation level. Adiponectin could improve the inhibition of myocardial autophagic flux induced by β <subscript>1</subscript> -AA partly dependent on AMPK, so as to provide an experimental basis for the treatment of patients with β <subscript>1</subscript> -AA-positive cardiac dysfunction.<br /> (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1582-4934
Volume :
25
Issue :
17
Database :
MEDLINE
Journal :
Journal of cellular and molecular medicine
Publication Type :
Academic Journal
Accession number :
34322993
Full Text :
https://doi.org/10.1111/jcmm.16807