A reducing environment stabilizes HIF-2α in SH-SY5Y cells under hypoxic conditions

Abstract 

Accumulating evidence suggests that hypoxia-inducible factor-2 (HIF-2) is important for the cellular response to hypoxia. However, it is not clear how HIF-2 is regulated under hypoxic conditions. We investigated kinetic changes in redox status and HIF-2α accumulation in hypoxic SH-SY5Y cells. Our results demonstrated that hypoxia caused a reducing environment and increased HIF-2α protein levels. Experiments with redox modulations (N-acetylcysteine and l-buthionine sulfoximine) confirmed that a reducing environment induced HIF-2α accumulation while an oxidizing environment decreased it. In addition, experiments with SOD mimic, catalase, and exogenous H₂O₂ provided evidence that the presence of H₂O₂ down-regulated the amount of HIF-2α protein. This study offers novel evidence supporting redox status regulation of HIF-2α accumulation under hypoxic conditions.

Abbreviations: BSO, l-buthionine sulfoximine, h, hours, HIF-2, hypoxia inducible factor 2, NAC, N-acetyl cysteine, ROS, reactive oxygen species

Keywords: HIF-2α, Hypoxia, Redox status, SH-SY5Y, Stroke, Brain tumor