title: SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain.
abstract: Our previous studies have shown that hyperbaric oxygen preconditioning (HBO-PC) induces tolerance to cerebral ischemia/reperfusion (I/R). This study aimed to investigate whether SirT1, a class III histone deacetylase, is involved in neuroprotection elicited by HBO-PC in animal and cell culture models of ischemia. Rats were subjected to middle cerebral artery occlusion for 120 minutes after HBO-PC (once a day for 5 days). Primary cultured cortical neurons were exposed to 2 hours of HBO-PC after 2 hours of oxygen-glucose deprivation (OGD). We showed that HBO-PC increased SirT1 protein and mRNA expression, promoted neurobehavioral score, reduced infarct volume, and improved morphology at 24 hours and 7 days after cerebral I/R. Neuroprotection of HBO-PC was attenuated by SirT1 inhibitor EX527 and SirT1 knockdown by short interfering RNA (siRNA), whereas it was mimicked by SirT1 activator resveratrol. Furthermore, HBO-PC enhanced SirT1 expression and cell viability and reduced lactate dehydrogenase release 24 hours after OGD/re-oxygenation. The neuroprotective effect of HBO-PC was emulated through upregulating SirT1 and, reversely, attenuated through downregulating SirT1. The modulation of SirT1 was made by adenovirus infection carrying SirT1 or SirT1 siRNA. Besides, SirT1 increased B-cell lymphoma 2 (Bcl-2) expression and decrease cleaved caspase 3. These results indicate that SirT1 mediates HBO-PC-induced tolerance to cerebral I/R through inhibition of apoptosis.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yan
authors.forename: Zongping
authors.initials: Z
authors.lastname: Fang
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Yang
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Chong
authors.initials: C
authors.lastname: Lei
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002227:Carbazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006931:Hyperbaric Oxygenation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C505410:Casp3 protein, rat; D053148:Caspase 3; C488368:Sirt1 protein, rat; D056564:Sirtuin 1