Astrocyte stellation induced by Rho kinase inhibitors in culture.
To understand the role of Rho kinases in regulation of astrocyte morphology, we investigated the effects of Rho kinase inhibitors on the morphology of cultured rat cortical astrocytes. Cultured astrocytes exhibited flattened, polygonal morphology in the absence of stimulation, but changed into process-bearing stellate cells following treatment with the selective Rho kinase inhibitor Y-27632 (1-10 microM). The Y-27632-induced astrocyte stellation was abolished by treatment with colchicine, indicating that the response requires reorganization of cytoskeletal elements. The effect of Y-27632 was mimicked by another Rho kinase inhibitor HA1077, but not by the protein kinase C inhibitor GF-109203X or the protein kinase A inhibitor KT5720. These results suggest that Rho kinases are in an activated state in the absence of stimuli and contribute to the maintenance of polygonal morphology of cultured astrocytes.
Abe
Kazuho
K
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. abe@hoshi.ac.jp
Misawa
Miwa
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002227:Carbazoles; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex; D003078:Colchicine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006074:Gout Suppressants / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides / Q000494:pharmacology; D010590:Phalloidine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D054460:rho-Associated Kinases
D000199:Actins; D000577:Amides; D002227:Carbazoles; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides; D011725:Pyridines; D011758:Pyrroles; C108830:Y 27632; D010590:Phalloidine; C057416:KT 5720; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C070515:bisindolylmaleimide I; C049347:fasudil; D003078:Colchicine