title: Neuroprotective effect of resveratrol on ischemia/reperfusion injury in rats through TRPC6/CREB pathways.
abstract: Previous studies have provided evidences that resveratrol can protect the brain from ischemia/reperfusion injury; the mechanisms of its neuroprotective effects remain unknown. To investigate whether resveratrol has neuroprotective effects on ischemia and reperfusion injury and whether resveratrol exerts its neuroprotective effects through inhibition of calpain proteolysis of TRPC6, a transient middle cerebral artery occlusion (MCAO) model was employed in rats. Western blot analysis was performed to detect the protein levels of aII-spectrin, transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated cAMP/Ca(2+) response element-binding protein (p-CREB). The immunoreactivity of p-CREB and TRPC6 were measured by quantum dot-based immunofluorescence analysis. Our results showed that MCAO rats showed large cortical infarct volumes and neurological scores. By contrast, resveratrol, when applied for 7 days before MCAO onset, significantly reduced infarct volumes and enhanced neurological scores at 24 h after reperfusion, and these results were accompanied by elevated TRPC6 and p-CREB activity and decreased calpain activity. When MEK or CaMKIV activity was inhibited by the addition of PD98059 or KN62, the neuroprotective effects of resveratrol were attenuated, and we observed a correlated decrease in CREB activity. Our results demonstrated that resveratrol prevented the brain from ischemia/reperfusion injury through the TRPC6-MEK-CREB and TRPC6-CaMKIV-CREB pathways.
authors: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.
authors: Yun
authors: Y
authors: Lin
authors: Fang
authors: F
authors: Chen
authors: Jiancheng
authors: J
authors: Zhang
authors: Tingting
authors: T
authors: Wang
authors: Xin
authors: X
authors: Wei
authors: Jing
authors: J
authors: Wu
authors: Yinglu
authors: Y
authors: Feng
authors: Zhongliang
authors: Z
authors: Dai
authors: Qingping
authors: Q
authors: Wu
mesh_terms: D000818:Animals; D002154:Calpain / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D002154:Calpain; D000077185:Resveratrol