首页|Endogenous reactive oxygen species and nitric oxide have opposite roles in regulating HIF-1alpha expression in hypoxic astrocytes
Endogenous reactive oxygen species and nitric oxide have opposite roles in regulating HIF-1alpha expression in hypoxic astrocytes
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Ischemic stroke results in cerebral tissue hypoxia and increased expression of hypoxia-inducible factor(HIF),which is critically implicated in ischemic brain injury.Understanding the mechanisms of HIF-1alpha regulation in the ischemic brain has been an important research focus.The generation of both nitric oxide(NO)and reactive oxygen species(ROS)is increased under hypoxic/ischemic conditions and each of them has been independently shown to regulate HIF-1alpha expression.In this study,we investigated the cross-effects of NO and ROS on the expression of HIF-1alpha in hypoxic astrocytes.Ex-posure of astrocytes to 2 h-hypoxia remarkably increased HIF-1alpha protein levels,which was accom-panied by increased NO and ROS production.Decreasing ROS with NAC,NADPH oxidase inhibitor DPI,or SOD mimetic MnTMPyP decreased hypoxia-induced HIF-1alpha protein accumulation and increased NO level in hypoxic astrocytes.The NO synthase(NOS)inhibitor L-NAME inhibited ROS generation,which led to a reduction in hypoxia-induced HIF-1alpha protein expression.Although NOS inhibitor or ROS scavengers alone reduced HIF-1alpha protein levels,the reduction was reversed when NOS inhib-itor and ROS scavenger present together.The NO scavenger PTIO increased hypoxia-induced HIF-1alpha protein expression and ROS production,while HIF-1alpha protein level was decreased in the presence of NO scavenger and ROS scavenger together.These results suggest that ROS,NO,and their interaction critically contribute to the regulation of hypoxia-induced HIF-1alpha protein accumulation under hypoxic condition.Furthermore,our results indicate that hypoxia-induced NO generation may represent an endogenous mechanism for balancing ROS-mediated hypoxic stress,as reflected by inhib-iting hypoxia-induced HIF-1alpha protein accumulation.
HypoxiaHypoxia-inducible factor 1AstrocyteNitric oxideReactive oxygen species
Qingquan Chen、Wenlan Liu、Xi Sun、Ke Jian Liu、Rong Pan
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Department of Pharmaceutical Sciences,University of New Mexico Health Sciences Center,Albuquerque,NM 87131,USA
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