Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction.
Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.
Yano
Kazuo
K
Laboratory for Pharmacology, Asahi Kasei Pharma, Shizuoka, Japan.
Kawasaki
Koh
K
Hattori
Tsuyoshi
T
Tawara
Shunsuke
S
Toshima
Yoshinori
Y
Ikegaki
Ichiro
I
Sasaki
Yasuo
Y
Satoh
Shin-ichi
S
Asano
Toshio
T
Seto
Minoru
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D002544:Cerebral Infarction / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D051700:Activating Transcription Factor 3; D000577:Amides; C497108:Atf3 protein, rat; D004791:Enzyme Inhibitors; D018994:Myosin Light Chains; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011725:Pyridines; D014020:Tissue Extracts; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil