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

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-2alpha accumulation in hypoxic SH-SY5Y cells. Our results demonstrated that hypoxia caused a reducing environment and increased HIF-2alpha protein levels. Experiments with redox modulations (N-acetylcysteine and l-buthionine sulfoximine) confirmed that a reducing environment induced HIF-2alpha 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-2alpha protein. This study offers novel evidence supporting redox status regulation of HIF-2alpha accumulation under hypoxic conditions.