Survival-promoting and protein kinase C-regulating roles of basic FGF for hippocampal neurons exposed to phorbol ester, glutamate and ischaemia-like conditions.
Recent evidence suggests that protein kinase C (PKC) is involved in the pathophysiology of neurodegenerative diseases. We examined the effect of basic fibroblast growth factor (bFGF) on the survival of cultured rat hippocampal neurons exposed to conditions in which PKC is likely to play a role. bFGF reduced neuron damage caused by the PKC-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), glutamate and ischaemia-like culture conditions. bFGF was able to counteract the excessive activation of PKC caused by these treatments. Moreover, bFGF prevented the loss of PKC occurring after prolonged exposure to TPA or ischaemia-like conditions. These results indicate that both the overactivation and the abnormal degradation of PKC can lead to neuron degeneration, and that the neurotrophic competence of bFGF may reside in its ability to regulate and normalize the PKC phosphorylating system.
Louis
J C
JC
Department of Biology, University of California at San Diego, La Jolla.
Magal
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Gerdes
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Seifert
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000595:Amino Acid Sequence; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005971:Glutamates; D007546:Isoquinolines; D010879:Piperazines; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate