Fibroblast growth factor 2 induces apoptosis in the early primary culture of rat cortical neurons.
In the central nervous system, fibroblast growth factor 2 (FGF2) is known to have important functions in cell survival and differentiation. In addition to its roles as a neurotrophic factor, we found that FGF2 caused cell death in the early primary culture of cortical neurons. FGF2-induced neuronal cell death showed apoptotic characters, e.g., chromatin condensation and DNA fragmentation. The ultrastructural morphology of FGF2-treated neurons indicated apoptotic features such as progressive cell shrinkage, blebbing of the plasma membrane, loss of cytosolic organelles, clumping of chromatin, and fragmentation of DNA. Tyrosine kinase inhibitors significantly rescued neurons from FGF2-induced apoptosis. FGF2 potentiated a marked influx of Ca(2+) into neurons before apoptosis. Both a calcium chelator and L-type voltage-sensitive Ca(2+) channel (L-VSCC) blockers attenuated FGF2-induced apoptosis, whereas other blockers of VSCCs such as N-type and P/Q-types did not. Blockers of L-VSCCs significantly suppressed FGF2-enhanced Ca(2+) influx into neurons. Moreover, FGF2 also generated reactive oxygen species (ROS) before apoptosis. Radical scavengers reduced not only the FGF2-generated ROS, but also the FGF2-induced Ca(2+) influx and apoptosis. In conclusion, we demonstrated that FGF2 caused apoptosis via L-VSCCs in the early neuronal culture.
Yagami
Tatsurou
T
Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo, 670-8524, Japan. yagami@himeji-du.ac.jp
Takase
Kenkichi
K
Yamamoto
Yasuhiro
Y
Ueda
Keiichi
K
Takasu
Nobuo
N
Okamura
Noboru
N
Sakaeda
Toshiyuki
T
Fujimoto
Masafumi
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2