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Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway

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单位： [1]Department of Respiratory and Critical Care Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China. [2]Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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关键词： Chronic intermittent hypoxia Autophagy Apoptosis Cardiomyocyte damage Calcineurin

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Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.Copyright © 2023. Published by Elsevier Inc.

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出版当年[2022]版：

大类 | 3 区医学

小类 | 4 区肿瘤学 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

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出版当年[2021]版：

Q3 CELL BIOLOGY Q3 ONCOLOGY

最新[2023]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子： 3.3 最新[2023版] 3.3 最新五年平均 4.145 出版当年[2021版] 4.253 出版当年五年平均 3.905 出版前一年[2020版] 3.7 出版后一年[2022版]

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第一作者单位： [1]Department of Respiratory and Critical Care Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China.

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