Fasudil protects cultured N1E-115 cells against lysophosphatidic acid-induced neurite retraction through inhibition of Rho-kinase.
The aim of this study was to investigate the possible effects of the Rho-kinase inhibitor, fasudil, on the lysophosphatidic acid (LPA)-induced neurite retraction in N1E-115 cells. In cultured N1E-115 cells, LPA produced a marked increase in the population of rounded cells. Fasudil or hydroxyfasudil, an active metabolite of fasudil, blocked cell rounding in a concentration-dependent manner at levels between 1 and 10 μM, with IC₅₀ values of 1.7 or 1.6 μM, respectively. Fasudil or hydroxyfasudil concentration-dependently inhibited phosphorylation of the myosin binding subunit of myosin phosphatase in N1E-115 cells. These results indicate that Rho-kinase is essential for LPA-induced neurite retraction in N1E-115 cells and that inactivation of Rho-kinase by a Rho-kinase inhibitor, such as fasudil, eliminates cell rounding and promotes neurite outgrowth, thus improving neurological function in the brain damage.
Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni-shi, Shizuoka 410-2321, Japan. sato.sn@om.asahi-kasei.co.jp
Shin-Ichi
S
Satoh
Koh
K
Kawasaki
Asako
A
Hitomi
Ichiro
I
Ikegaki
Toshio
T
Asano
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line / Q000187:drug effects*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D008246:Lysophospholipids; D047428:Protein Kinase Inhibitors; C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C032881:lysophosphatidic acid; C049347:fasudil