title: SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22.
abstract: The aim of this study was to investigate whether the SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury (CIRI) via targeting p53/microRNA-22. We found that the overexpression of sirtuin 1 (SIRT1) decreased the infarct volume, suppressed p53 protein expression and activated microRNA-22 expression following CIRI. An injection of lipopolysaccharide (LPS, 1 mg/ml; Sigma, St. Louis, MO USA) into the corpus callosum was used to induce CIRI in rats. The infarct volume and neurological deficit score were used to examine the effects of SIRT1 on CIRI. Furthermore, the overexpression of SIRT1 was found to suppress caspase-3 activity, inhibit the activation of the Bax signaling pathway, reduce tumor necrosis factor-α (TNF-α) and interleukin (IL)-6) activity, decrease cyclooxygenase (COX)‑2 and inducible nitric oxide synthase (iNOS) protein expression, and increase IL-10 activity following CIRI. Following the downregulation of SIRT1, p53 protein expression was significantly increased, microRNA-22 expression was inhibited, caspase-3 activity was increased and the Bax signaling pathway was activated. In addition, the activity of TNF-α and IL-6 was was enhanced, COX-2 and iNOS protein expression was increased, and IL-10 activity was reduced following CIRI. Thus, the data from our study suggest that SIRT1 attenuates CIRI by targeting the p53/microRNA-22 axix, while suppressing apoptosis, inflammation, COX-2 and iNOS expression.
authors.affiliation: Department of Neurology, Cangzhou Central Hospital, Hebei 060000, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Beijing 100010, P.R. China.
authors.forename: Bincheng
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D001549:Benzamides; C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; D009284:Naphthols; D018696:Neuroprotective Agents; D016159:Tumor Suppressor Protein p53; C439060:sirtinol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053148:Caspase 3; D056564:Sirtuin 1