HIF-1α enhances autophagy to alleviate apoptosis in marginal cells in the stria vascular in neonatal rats under hypoxia. (August 2022)

• Record Type: Journal Article
• Authors: Huang, Sihan; Zhao, Yanyun; Liu, Jun
• Is Part Of: International journal of biochemistry & cell biology. Volume 149(2022)
• Publication Date: 2022-08
• Subjects: Hypoxia -- HIF-1α -- Autophagy -- BNIP3 -- Apoptosis -- Cochlea; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2022.106259
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: In the cochlea, various factors, such as noise, aging, and inflammation, induce hypoxia, resulting in the up-regulation of hypoxia inducible factor-1α (HIF-1α). The role of HIF-1α in hypoxic marginal cells (MCs) of the stria vascularis is unknown. This study examined HIF-1α-mediated autophagy in MCs of neonatal rats and its mechanism of action. We found that an increase in HIF-1α expression was associated with autophagy and apoptosis. Treatment with PX478, a specific inhibitor of HIF-1α, decreased the HIF-1α level, and the degree of autophagy decreased in hypoxic and apoptotic MCs. By contrast, treatment with DMOG, an activator of HIF-1α, increased autophagy and decreased apoptosis. Both PX478 and DMOG had no effect on the apoptotic rate after treatment with 3-methyladenine, an inhibitor of autophagy, indicating that HIF-1α promoted autophagy to protect MCs from hypoxia-induced apoptosis. Lastly, we silenced Bnip3(Bcl-2/adenovirus E1B 19-kDa interacting protein) in MCs to identify the mechanism of action. Our results show that the HIF-1α–BNIP3 pathway mediates the anti-apoptotic effects through an increase in autophagy.