PI3K-AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by MitoKATP-Mediated Mitochondrial Translocation of pAKT

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Hua-Pei SongQiong Zhang

Abstract

The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an important intracellular signal pathway in regulating cell proliferation, differentiation and apoptosis. In previous studies, we've demonstrated that PI3K-AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis through mitochondrial function. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined. Here, we addressed this question. Cardiomyocytes were exposed to hypoxia, with/without different inhibitors and then protein levels were assessed by Western blotting. We found that the PI3K-AKT pathway was activated in cardiomyocytes that were exposed to hypoxia. Moreover, the phospho-AKT (pAKT) translocated from cytosol to mitochondria via mitochondrial adenosine triphosphate-dependent potassium (mitoKATP), leading to an increase in cytochrome c oxidase (CcO) activity to suppress apoptosis. On the other hand, the mitoKATP specific blocker, 5-hydroxydecanote (5-HD), or suppression of CcO using siRNA, inhibited the pAKT mitochondrial translocation to maintain the CcO activity, resulting in mitochondrial dysfunction and cellular apoptosis induced by hypoxia. These findings suggest that the anti-apo...Continue Reading

Citations

May 6, 2019·European Journal of Human Genetics : EJHG·María Elena Rodríguez-GarcíaFrancisco Martínez-Azorín
Mar 20, 2019·Journal of Cellular Biochemistry·Shengzhong LiuYingqiang Guo
Aug 3, 2019·European Journal of Medicinal Chemistry·Lucia BiasuttoMario Zoratti
May 14, 2021·Circulation Research·Gary D LopaschukE Dale Abel
Aug 17, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Rasha M S M MohamedDalia M Abd El Motteleb
Aug 28, 2021·International Journal of Molecular Sciences·Siarhei A DabravolskiAlexander N Orekhov
Aug 20, 2021·Journal of Thrombosis and Haemostasis : JTH·Weiyu ZhaoWen Huang

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