title: Mechanism of Mitochondrial Connexin43's Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury.
abstract: We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. houshuai0310@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. blush135@163.com.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Shen
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. zhaommchn@163.com.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhao
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. liuxiuping12345@163.com.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Liu
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. xiehy321@163.com.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Xie
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. dengfang1212@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Neurology and Neuroscience center, the First Hospital of Jilin University, Changchun 130021, China. fengjcfrank@126.com.
authors.forename: Jia-Chun
authors.initials: JC
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D018031:Connexin 43; D024101:Mitochondrial Proteins; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D011493:Protein Kinase C
keywords: cerebral ischemia-reperfusion; mitochondria; mitochondrial ATP-sensitive K+ channel; mitochondrial connexin43; protein kinase C