Fasudil protects cultured N1E-115 cells against lysophosphatidic acid-induced neurite retraction through inhibition of Rho-kinase

• Published in: Brain research bulletin Vol. 84; no. 2; pp. 174 - 177
• Main Authors: Satoh, Shin-Ichi, Kawasaki, Koh, Hitomi, Asako, Ikegaki, Ichiro, Asano, Toshio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2011
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Animals; Cell Line - drug effects; Fasudil; Humans; Lysophosphatidic acid; Lysophospholipids - pharmacology; Mice; N1E-115 cell; Neurite retraction; Neurites - drug effects; Neurites - ultrastructure; Neurology; Neurons - cytology; Protein Kinase Inhibitors - pharmacology; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Rho-kinase; Rho-kinase; Lysophosphatidic acid; Neurite retraction; N1E-115 cell; Fasudil
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2010.11.013

Abstract 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.