A reducing environment stabilizes HIF-2α 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-2 alpha accumulation in hypoxic SH-SY5Y cells. Our results demonstrated that hypoxia caused a reducing environment and increased HIF-2 alpha protein levels. Experiments with redox modulations (N-acetylcysteine and L-buthionine sulfoximine) confirmed that a reducing environment induced HIF-2 alpha accumulation while an oxidizing environment decreased it. In addition, experiments with SOD mimic, catalase, and exogenous H(2)O(2) provided evidence that the presence of H(2)O(2) down-regulated the amount of HIF-2 alpha protein. This study offers novel evidence supporting redox status regulation of HIF-2 alpha accumulation under hypoxic conditions. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.