HIF-1α enhances autophagy to alleviate apoptosis in marginal cells in the stria vascular in neonatal rats under hypoxia

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.

Keywords: Apoptosis; Autophagy; BNIP3; Cochlea; HIF-1α; Hypoxia.