Insulin or bFGF and C2 ceramide increase newborn rat retinal ganglion cell survival rate.
Treatment of RGCs with insulin or C2 ceramide alone increased survival rate by 30%. Adding both insulin and C2 ceramide increased survival rate by 80%. Protein phosphatase 2A (PP2A) inhibitor okadaic acid (OA) eliminated the effect of C2 ceramide, but not that of insulin. Protein kinase inhibitor K252a decreased the effect of C2 ceramide in a dose-dependent manner, but the effect of insulin was not changed. Treatment of RGCs with bFGF increased survival rate by 36%. Adding both bFGF and C2 ceramide increased survival rate by 102%. OA did not alter the effect of bFGF, whereas K252a increased survival rate in a dose-dependent manner. Inhibition of C2 ceramide by OA suggests that PP2A activation is involved in its pathway, whereas PP2A is not involved in the insulin- and bFGF-activated pathway. Elimination of the effect of C2 ceramide by K252a suggests that sphingomyelin cycle activation is mediated by a protein kinase not important in the insulin-activated pathway. Moreover, the increased effect of bFGF and dose-dependently decreased effect of C2 ceramide by K252a suggest that different protein kinases are important in bFGF- and ceramide-mediated enhancement of RGC survival rate.
Ito
Mami
M
Department of Ophthalmology, Hiroshima University, School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. mami@saitama-med.ac.jp
D000818:Animals; D000831:Animals, Newborn; D002227:Carbazoles / Q000494:pharmacology; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D026121:Indole Alkaloids; D007328:Insulin / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007328:Insulin; C064769:N-acetylsphingosine; D016222:Fibroblast Growth Factor 2; D019319:Okadaic Acid; C049985:staurosporine aglycone; D013110:Sphingosine