Hypoxia-inducible factor 1 contributes to N-acetylcysteine's protection in stroke.

Hypoxia-inducible factor 1 contributes to N-acetylcysteine's protection in stroke. Free Radic Biol Med. 2013 Nov 29; Authors: Zhang Z, Yan J, Taheri S, Liu J, Shi H Abstract Stroke is a leading cause of adult morbidity and mortality with very limited treatment options. Evidence from pre-clinical models of ischemic stroke has demonstrated that the antioxidant N-acetylcysteine (NAC) effectively protects the brain from ischemic injury. Here, we evaluated a new pathway through which NAC exerted its neuroprotection in a transient cerebral ischemia animal model. Our results demonstrated that pre-treatment of NAC increased protein levels of hypoxia-inducible factor-1α (HIF-1α), the regulatable subunit of HIF-1, and its target proteins erythropoietin (EPO) and glucose transporter (GLUT)-3 in the ipsilateral hemispheres of rodents subjected to 90min middle cerebral artery occlusion (MCAO) and 24h reperfusion. Interestingly, after NAC pretreatment and stroke, the contralateral hemisphere also demonstrated increased levels of HIF-1α, EPO, and GLUT3, but to a less extent. Suppressing HIF-1 activity by two widely used pharmacological inhibitors, YC-1 and 2ME2, and specific knock-out of neuronal HIF-1α abolished NAC's neuroprotective effects. The results also showed that YC-1 and 2ME2 massively enlarged infarcts, indicating their toxic effect was larger than just abolishing NAC's neuroprotective effects. Furthermore, we determined the mechanism of NAC-m...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research