title: Induction of inducible nitric oxide synthase by isoflurane post-conditioning via hypoxia inducible factor-1α during tolerance against ischemic neuronal injury.
abstract: Recent studies have shown that isoflurane protects against ischemic injury via inducible nitric oxide synthase (iNOS). Hypoxia inducible factor (HIF)-1α is a transcriptional factor that activates after cerebral ischemia. However, whether iNOS gene containing the sequence of the hypoxia response element (HRE) is a HIF-1α target during tolerance against ischemic neuronal injury induced by isoflurane post-conditioning remains unknown. In this study, we report that HIF-1α and iNOS gene expression were augmented after cerebral ischemia in rats. Furthermore, isoflurane post-conditioning resulted in greater accumulation of HIF-1α and iNOS gene expression, following by HIF-1α transcriptional activity enhancement and co-localization of HIF-1α and iNOS. Accordingly, in the primary cortical neuron cultures, silencing of HIF-1α attenuated the accumulation of iNOS and the protective effects of isoflurane post-conditioning. Our results suggest the involvement of HIF-1α in the regulation of iNOS during tolerance against cerebral ischemia induced by isoflurane post-conditioning, which provide a mechanistic basis of novel therapeutic strategies for ischemic stroke.
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Fang Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002478:Cells, Cultured; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D057775:Ischemic Postconditioning / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II