AMPK blunts chronic heart failure by inhibiting autophagy

Bioscience Reports
Yanhui LiChen Liu

Abstract

AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, has been shown to exert a protective effect against cardiac hypertrophy and heart failure. Our previous reports have demonstrated that AMPK can inhibit cardiac hypertrophy and block the development of heart failure by promoting autophagy. However, other investigators have demonstrated that overactive and dysregulated autophagy may also contribute to the onset and exacerbation of heart failure. Thus, a major goal of the present investigation is to explore how AMPK regulates autophagy in heart failure. First, heart failure was induced in mice by 4 weeks of pressure overload; AMPK activation was subsequently induced by injecting 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleotide (AICAR) after the establishment of chronic heart failure. We showed that AMPK activation significantly attenuated the progression of heart failure and improved cardiac function, which was accompanied by decreased autophagy levels in the failing hearts. Additionally, we demonstrated that the treatment with AICAR inhibited phosphorylation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) downstream effectors 4E-binding protein1 (4EBP1), and ribosomal protein S6 kinase (p70S...Continue Reading

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Citations

Feb 9, 2020·Cardiovascular Drugs and Therapy·Kerstin N Timm, Damian J Tyler
Feb 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Serge HardyMichel L Tremblay
Aug 16, 2019·Bioscience Reports·Jia LiuJiyan Leng
Mar 3, 2020·Frontiers in Pharmacology·Yun ChenGuoliang Meng
Feb 7, 2021·Current Treatment Options in Oncology·Michele RussoAlessandra Ghigo
Dec 22, 2020·Frontiers in Cell and Developmental Biology·Jing-Li XuJiang-Jiang Qin
May 7, 2021·Cardiovascular Research·Damián GaticaDaniel J Klionsky

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Methods Mentioned

BETA
Protein Assay
X-ray
electron microscopy

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