Mechanism of Mitochondrial Connexin43's Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

被引:16
作者
Hou, Shuai
Shen, Ping-Ping
Zhao, Ming-Ming
Liu, Xiu-Ping
Xie, Hong-Yan
Deng, Fang
Feng, Jia-Chun [1 ]
机构
[1] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Peoples R China
基金
中国国家自然科学基金;
关键词
mitochondrial connexin43; mitochondria; cerebral ischemia-reperfusion; mitochondrial ATP-sensitive K+ channel; protein kinase C; PROTEIN-KINASE-C; ISCHEMIA/REPERFUSION INJURY; CARDIOMYOCYTE MITOCHONDRIA; RISK-FACTORS; K+ CHANNELS; PKC; PHOSPHORYLATION; HYPOXIA; CARBENOXOLONE; DIAZOXIDE;
D O I
10.3390/ijms17050679
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:16
相关论文
共 38 条
[1]   Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43 [J].
Azarashvili, Tamara ;
Baburina, Yulia ;
Grachev, Dmitry ;
Krestinina, Olga ;
Evtodienko, Yuri ;
Stricker, Rolf ;
Reiser, Georg .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2011, 300 (03) :C707-C720
[2]   Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning [J].
Boengler, K ;
Dodoni, G ;
Rodriguez-Sinovas, A ;
Cabestrero, A ;
Ruiz-Meana, M ;
Gres, P ;
Konietzka, I ;
Lopez-Iglesias, C ;
Garcia-Dorado, D ;
Di Lisa, F ;
Heusch, G ;
Schulz, R .
CARDIOVASCULAR RESEARCH, 2005, 67 (02) :234-244
[3]   CHARACTERIZATION OF PROTEIN-KINASE-C ISOTYPE EXPRESSION IN ADULT-RAT HEART - PROTEIN-KINASE C-EPSILON IS A MAJOR ISOTYPE PRESENT, AND IT IS ACTIVATED BY PHORBOL ESTERS, EPINEPHRINE, AND ENDOTHELIN [J].
BOGOYEVITCH, MA ;
PARKER, PJ ;
SUGDEN, PH .
CIRCULATION RESEARCH, 1993, 72 (04) :757-767
[4]   Hypoxia causes connexin 43 internalization in neonatal rat ventricular myocytes [J].
Danon, Asaf ;
Zeevi-Levin, Naama ;
Pinkovich, Dani Y. ;
Michaeli, Tomer ;
Berkovich, Alexander ;
Flugelman, Moshe ;
Eldar, Yonina C. ;
Rosen, Michael R. ;
Binah, Ofer .
GENERAL PHYSIOLOGY AND BIOPHYSICS, 2010, 29 (03) :222-233
[5]   Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning [J].
Ferdinandy, Peter ;
Schulz, Rainer ;
Baxter, Gary F. .
PHARMACOLOGICAL REVIEWS, 2007, 59 (04) :418-458
[6]   Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning [J].
Ferdinandy, Peter ;
Hausenloy, Derek J. ;
Heusch, Gerd ;
Baxter, Gary F. ;
Schulz, Rainer .
PHARMACOLOGICAL REVIEWS, 2014, 66 (04) :1142-1174
[7]  
FLAMENG W, 1980, J THORAC CARDIOV SUR, V79, P413
[8]  
Garlid KD, 1997, CIRC RES, V81, P1072
[9]   ATP-SENSITIVE K+ CHANNEL IN THE MITOCHONDRIAL INNER MEMBRANE [J].
INOUE, I ;
NAGASE, H ;
KISHI, K ;
HIGUTI, T .
NATURE, 1991, 352 (6332) :244-247
[10]   Cardiac connexins and impulse propagation [J].
Jansen, John A. ;
van Veen, Toon A. B. ;
de Bakker, Jacques M. T. ;
van Rijen, Harold V. M. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2010, 48 (01) :76-82