title: Acute resveratrol treatment modulates multiple signaling pathways in the ischemic brain.
abstract: Resveratrol has several beneficial effects, including reductions of oxidative stress, inflammatory responses and apoptosis. It has been known that resveratrol is a sirtuin 1 (SIRT1) activator and protective effects of resveratrol are mediated by Akt and mitogen-activated protein kinases. However, it is not examined whether these pathways are regulated by resveratrol in the ischemic brain. Previously, we found that acute resveratrol treatment reduces brain injury induced by transient focal ischemic stroke. In the present study, we defined the signaling pathways modulated by resveratrol in ischemia by examining SIRT1 expression and phosphorylation of Akt, ERK1/2 and p38 in the ischemic cortex. Resveratrol increased expression of SIRT1 and phosphorylation of Akt and p38 but inhibited the increase in phosphorylation of ERK1/2. Gene and protein levels of peroxisome proliferator-activated receptor γ coactivator 1α, a downstream molecule of SIRT1, and mRNA levels of its target genes antioxidative superoxide dismutase 2 and uncoupling protein 2 were elevated. Resveratrol also increased phosphorylation of cyclic AMP-response-element-binding protein and transcription of the anti-apoptotic gene Bcl-2. These results suggest that various neuroprotective actions of resveratrol, including anti-oxidative, anti-apoptotic and inflammatory effects, are mediated via modulation of multiple signaling pathways in the ischemic brain.
authors.affiliation: Department of Pharmacology, School of Medicine, Ewha Medical Research Institute, Ewha Womans University, 911-1 Mok6dong, Yangcheon-gu, Seoul 158-710, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Shin
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Park
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; D011494:Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol