Endostatin expression in neurons during the early stage of cerebral ischemia is associated with neuronal apoptotic cell death in adult hypertensive rat model of stroke.
Endostatin (ES) has been recognized as a potent anti-angiogenic factor. We here investigated the expression of ES in ischemic brain and the consequence of cells expressing ES after stroke in adult stroke-prone renovascular hypertensive rats. A single dose of Ca-074ME, a membrane-permeable cathepsin B (CB) specific inhibitor, or vehicle was given by intraperitoneal injection immediately after distal middle cerebral artery occlusion (dMCAO), ES expression was evaluated using fluorescent immunohistochemistry staining, and CB enzyme activity was tested by measuring the free 7-amino-4-methylcoumarin (AMC) released by CB from its' specific substrate, the Z-Arg-Arg-7-amido-4-methylcoumarin. ES immunoreactivity (IR) was significantly up-regulated as early as 6 h and returned to baseline level at 3 days in peri-infarct area following dMCAO. Double-staining experiment revealed that the majority of ischemia-induced ES positive cells were neurons. Furthermore, ES was co-labeled with CB and Cleaved Caspase-3(Asp175) whereas treatment with Ca-074ME reduced up-regulation of ES expression and attenuated apoptosis in peri-infarct neurons. Collectively, our data suggest that peri-infarct neurons express ES during the early stage of cerebral ischemia and treatment with Ca-074ME attenuates ES expression and apoptosis in peri-infarct neurons.
Hou
Qinghua
Q
Department of Neurology and stroke center, First affiliated Hospital, Sun Yat-Sen University, No 58 Zhongshan Road 2, Guangzhou 510080, PR China.
Ling
Li
L
Wang
Fang
F
Xing
Shihui
S
Pei
Zhong
Z
Zeng
Jinsheng
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D043169:Endostatins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors
C400541:CA 074 methyl ester; D003374:Coumarins; D004151:Dipeptides; D043169:Endostatins; D004791:Enzyme Inhibitors; C505410:Casp3 protein, rat; D053148:Caspase 3; D002401:Cathepsin B; C533916:Ctsb protein, rat; C028743:7-amino-4-methylcoumarin