Activin exerts a neurotrophic effect on cultured hippocampal neurons.
Activin is a member of the transforming growth factor (TGF)-beta superfamily, which comprises a growing list of multifunctional proteins that serve as regulators of cell proliferation and differentiation. Recently, activin was shown to regulate the neurotransmitter phenotype in peripheral neurons. It is also a potent survival factor for neurogenic clonal cell lines, retinal neurons and midbrain dopaminergic neurons. We have studied the effect of activin on hippocampal cells which show abundant expression of activin receptors or binding sites. Exposure of primary cultures of rat hippocampal neurons to activin supported neuronal survival. This neurotrophic action of activin was blocked by treatment with the tyrosine kinase inhibitor genistein or the protein kinase C inhibitor calphostin C. However, the Ca2+/calmodulin kinase inhibitor KN-62 had no effect. Nicardipine, a blocker of the L-type Ca2+ channel, also inhibited the neurotrophic effect of activin. Furthermore, activin potentiated the depolarization-induced elevation in intracellular Ca2+ concentration ([Ca2+]i). The neurotrophic effect and the potentiation of depolarization-induced increase of [Ca2+]i caused by activin were completely abolished by the protein synthesis inhibitor cycloheximide. These results suggest that activin supports neuronal survival by increasing the expression of voltage-dependent Ca2+ channel through the action of a tyrosine kinase and of protein kinase C, but not of Ca2+/calmodulin kinase.
Iwahori
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
Saito
H
H
Torii
K
K
Nishiyama
N
N
D028341:Activins; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D007265:Inhibins / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D009414:Nerve Growth Factors; D028341:Activins; D007265:Inhibins; D009529:Nicardipine