Abstract WMP70: HIF-1alpha Sumoylation Provides Neuroprotection in Ischemic Stroke
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional factor that regulates the cellular adaptive response to hypoxia and has been suggested as a potent therapeutic target in stroke. To find new post-transpational modification pathways of HIF-1 in ischemic brain, we determined SUMOylation of HIF-1α protein in ischemic brain of a rat middle cerebral artery occlusion (MCAO) stroke model. The results demonstrated that SUMOylation of HIF-1α by SUMO1 was increased in the ischemic brain. Immunostaining images showed that HIF-1α co-localized with SUMO1 in the neuron nucleus of the ischemic brain. Inhibition of HIF-1α SUMOylation by Ubc9 siRNA reduced HIF-1α protein level in primary neurons during hypoxia. Furthermore, ischemia-induced neuron death was increased by the Ubc9 siRNA. The results, for the first time, demonstrate that HIF-1α is directly SUMOylated in the ischemic brain. HIF-1α SUMOylation is important for HIF-1α stability and neuron survival during ischemia. These results complement the knowledge about HIF-1 regulation in ischemic brain and shed new light on the role of HIF-1 as a stroke therapeutic target.
- © 2012 by American Heart Association, Inc.