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Honokiol ameliorates angiotensin II‐induced cardiac hypertrophy by promoting dissociation of the Nur77–LKB1 complex and activating the AMPK pathway.

Authors :
Lin, Xiaoyan
Zhang, Hailin
Chu, Yong
Zhang, Yuze
Xu, Changsheng
Xie, Hong
Ruan, Qinyun
Lin, Jinxiu
Huang, Chun‐Kai
Chai, Dajun
Source :
Journal of Cellular & Molecular Medicine; Jan2024, Vol. 28 Issue 1, p1-18, 18p
Publication Year :
2024

Abstract

Pathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)‐mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)‐induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague–Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II‐induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II‐induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II‐induced Nur77 expression at the transcriptional level and promoted ubiquitination‐mediated degradation of Nur77, leading to dissociation of the Nur77–LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1‐AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77–LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1‐AMPK pathway to protect against cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15821838
Volume :
28
Issue :
1
Database :
Complementary Index
Journal :
Journal of Cellular & Molecular Medicine
Publication Type :
Academic Journal
Accession number :
175009695
Full Text :
https://doi.org/10.1111/jcmm.18028