BDNF and NT-3 but not CNTF counteract the Ca2+ ionophore-induced apoptosis of cultured cortical neurons: involvement of dual pathways.
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.
Takei
N
N
Department of Applied Biology, Kyoto Institute of Technology, Sakyo, Japan. nobtak@bri.niigata-u.ac.jp
Tanaka
O
O
Endo
Y
Y
Lindholm
D
D
Hatanaka
H
H
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D020934:Ciliary Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D000077191:Wortmannin
D000730:Androstadienes; D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D015759:Ionomycin; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin