title: Extracellular pH regulates autophagy via the AMPK-ULK1 pathway in rat cardiomyocytes.
abstract: 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.
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xupin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jiezhi
authors.initials: J
authors.lastname: Jia
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China. dxzhangswh@163.com.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China. yshuangtmmu@163.com.
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D011522:Protons; D000071189:Autophagy-Related Protein-1 Homolog; C586255:ULK1 protein, rat; D055372:AMP-Activated Protein Kinases
keywords: Unc-51-like kinase 1; adenosine monophosphate-activated protein kinase; autophagy; cardiomyocytes; pH