Effects of Oxidative Stress on Hypoxia Inducible Factor Expression in Ischemic Neurons

摘要

Cerebral ischemia (stroke) is a cause of substantial morbidity and mortality, and effective molecular therapies are being intensively sought. Hypoxia inducible factors (HIF) are important regulators of the hypoxic response, making modulation of HIF activity an attractive approach for the treatment of ischemic disease. Many studies have suggested that brain ischemia leads to the abnormal production of free radicals, which results in cell death. We investigated the effect of oxidative stress on HIF expression with in vitro ischemic models. Our results demonstrated that redox status could regulate not only the expression of HIF-la but also HIF-2a under low oxygen conditions. Furthermore, we found that redox status affected the level of erythropoietin, a downstream gene of HIF and a neuroprotective agent.