Fibroblast growth factor protects nitric oxide-induced apoptosis in neuronal SHSY-5Y cells.
Fibroblast growth factor (FGF) has been shown to protect tissue damage in animal models of cerebral and myocardial ischemia. The cellular and molecular mechanisms of FGF effects have not been fully defined. In the present study, we have investigated the effect of FGF homologs on nitric oxide (NO)-mediated neuronal cell death. Addition of NO donor S-nitroso-N-acetylpenicillamine (SNAP) to cultures of human neuroblastoma SHSY-5Y cells resulted in a concentration-dependent cell death. TdT-mediated dUTP-X nick end labeling and oligonucleosome assays confirmed that NO-mediated cell death occurred through the apoptotic pathway. In the presence of 150 microM SNAP, about 40% of the cells in culture underwent apoptosis. Treatment with FGF-2 resulted in greater than 80% reduction in NO-induced cell death. FGF addition to cell cultures also enhanced cell survival without affecting cell proliferation. FGF-2 effectively inhibited NO-mediated apoptosis even when added 6 h after treatment with SNAP. Examination of other homologs of FGF on NO-mediated cell death showed that in SHSY-5Y cells, FGF-2 and FGF-4, but not other FGF homologs, inhibited NO-mediated apoptosis. These results show that FGF-2 was a potent cell survival factor and protected SHSY-5Y cells from NO-mediated apoptosis. These effects were limited to FGF-2 and FGF-4 homologs.
Wagle
A
A
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Singh
J P
JP
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018696:Neuroprotective Agents; C110881:S-nitro-N-acetylpenicillamine; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D010396:Penicillamine