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Extracellular pH regulates autophagy via the AMPK–ULK1 pathway in rat cardiomyocytes
Author(s) -
Zhao Liping,
Cui Lin,
Jiang Xupin,
Zhang Junhui,
Zhu Minghua,
Jia Jiezhi,
Zhang Qiong,
Zhang Jiaping,
Zhang Dongxia,
Huang Yuesheng
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12359
Subject(s) - ampk , autophagy , pi3k/akt/mtor pathway , ulk1 , protein kinase a , microbiology and biotechnology , extracellular , chemistry , adenosine monophosphate , adenosine , mechanistic target of rapamycin , amp activated protein kinase , kinase , phosphorylation , signal transduction , biochemistry , biology , apoptosis
Various pathological conditions contribute to pH fluctuations and affect the functions of vital organs such as the heart. In this study, we show that in rat cardiomyocytes, acidic extracellular pH (pHe) inhibits autophagy, whereas alkaline pHe stimulates it. We also find that adenosine monophosphate‐activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc‐51‐like kinase 1 (ULK1) are very sensitive to pHe changes. Furthermore, by interfering with AMPK, mTOR or ULK1 activity, we demonstrate that the AMPK–ULK1 pathway, but not the mTOR pathway, plays a crucial role on pHe‐regulated autophagy and cardiomyocyte viability. These data provide a potential therapeutic strategy against cardiomyocyte injury triggered by pH fluctuations.