PMID- 10218870 OWN - NLM STAT- MEDLINE DCOM- 19990624 LR - 20191210 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 38 IP - 2 DP - 1999 Feb TI - BDNF and NT-3 but not CNTF counteract the Ca2+ ionophore-induced apoptosis of cultured cortical neurons: involvement of dual pathways. PG - 283-8 AB - The effect of neurotrophic factors on apoptosis induced by ionomycin, a potent Ca2+ ionophore, was investigated using cultured cortical neurons from embryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 (NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manner. In contrast to the neurotrophins, cilliary neurotrophic factor (CNTF) did not rescue neurons from cell death induced by ionomycin. The protective effect of BDNF was partially blocked by wortmannin, a phosphatidylinositol 3-kinase inhibitor, and by PD98059, a MAP kinase kinase inhibitor. However, the addition of both compounds together completely inhibited the survival promoting effect of BDNF. These results suggest that the neuroprotective effect of BDNF requires activation of both phosphatidylinositol-3 kinase and the Ras/MAP kinase cascade and that CNTF signaling through other pathways is without an effect in this system. FAU - Takei, N AU - Takei N AD - Department of Applied Biology, Kyoto Institute of Technology, Sakyo, Japan. nobtak@bri.niigata-u.ac.jp FAU - Tanaka, O AU - Tanaka O FAU - Endo, Y AU - Endo Y FAU - Lindholm, D AU - Lindholm D FAU - Hatanaka, H AU - Hatanaka H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Androstadienes) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protein Kinase Inhibitors) RN - 56092-81-0 (Ionomycin) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) RN - XVA4O219QW (Wortmannin) SB - IM MH - Androstadienes/pharmacology MH - Animals MH - Apoptosis/drug effects/*physiology MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Cerebral Cortex/*cytology MH - Ciliary Neurotrophic Factor MH - Dose-Response Relationship, Drug MH - Embryo, Mammalian MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Ionomycin/*pharmacology MH - Mitogen-Activated Protein Kinase Kinases MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/*pharmacology MH - Neurons/*cytology/drug effects/*physiology MH - Neuroprotective Agents/pharmacology MH - Neurotrophin 3 MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinase Inhibitors MH - Rats MH - Rats, Wistar MH - Wortmannin EDAT- 1999/04/28 00:00 MHDA- 1999/04/28 00:01 CRDT- 1999/04/28 00:00 PHST- 1999/04/28 00:00 [pubmed] PHST- 1999/04/28 00:01 [medline] PHST- 1999/04/28 00:00 [entrez] AID - S0028390898001890 [pii] AID - 10.1016/s0028-3908(98)00189-0 [doi] PST - ppublish SO - Neuropharmacology. 1999 Feb;38(2):283-8. doi: 10.1016/s0028-3908(98)00189-0.