| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Satoshi Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (20266779)
NAKAJIMA Hiroshi Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80227800)
HORI Tomokatsu Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (60010443)
YAMAGUCHI Tomoko Tokyo Women's Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (90075276)
MITSUYAMA Tetsuryu Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80318104)
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| Research Abstract |
bFGF at 1-100 ng/ml promoted cell viability dose-4ejendently up to 200% following 24 hours incubation under control culture condition in PC12 cells. Furthermore, preincubation for 24 hours with 1-100 ng/ml of bFGF prevented cell death induced by A23 187 treatment up to 30-40% in a dose-dependent manner in PC12 cells. In both experiments bFGF was effective on cell survival and protection against apoptosis to the same extent as NGF.
In the western blot analysis, bFGF activated Ras, PI3-kinase, and Bcl-2 in various degrees and at various time points. Ras was upregulated dominantly in the early stage up to 24 hours following bFGF stimulation returning to the level of baseline at 48 hours. On the other hand, PI3-kinase was activated in the later phase at 48 hours compared to 24 hours as a cellular response to bFGF. In the current study, however, Bcl-2, a major candidate molecule to suppress programmed cell death in various cell types, was upregulated less appreciably than Ras or PI3-kinase.
As controls, sodium and calcium did not induce cell death. On the other hand, 15 mM potassium induced cell death within five minutes, and bFGF prevented it.
In the experiments with inhibitors of intracellular signaling pathways, U0126 and PD98059, MEK-1, -2 inhibitors, inhibited protective effect of bFGF on cell survival. Furthermore, the MEK 1 and 2 specific inhibitors suppressed cell survival in order of bFGF, EGF, and NGF dose-dependently. The effect of NGF on cell survival was strongly suppressed compared with bFGF and EGF.
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