RRC ID 39002
Author Tanaka J, Koshimura K, Murakami Y, Sohmiya M, Yanaihara N, Kato Y.
Title Neuronal protection from apoptosis by pituitary adenylate cyclase-activating polypeptide.
Journal Regul Pept
Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to have trophic effects on neurons. Apoptosis of PC12 cells was induced by depletion of serum and nerve growth factor (NGF) from culture medium. Not only high potassium-induced Ca2+ channel activation but PACAP-38 at physiological concentrations (10[-10] to 10[-8] M) protected PC12 cells from apoptosis. PACAP-38 increased Ca2+ uptake and intracellular Ca2+ concentrations in PC12 cells. The effects of PACAP-38 on cell survival and Ca2+ channels were eliminated by inhibitors for Ca2+ channels and protein kinase A, and mimicked by 8-bromo-cAMP. Mitogen-activated protein (MAP) kinase activity was stimulated by PACAP-38. These findings implicate that PACAP protects PC12 cells from apoptosis by activating Ca2+ channels via the cAMP-protein kinase A pathway to stimulate MAP kinase cascade.
Volume 72(1)
Pages 1-8
Published 1997-9-26
DOI 10.1016/s0167-0115(97)01038-0
PII S0167-0115(97)01038-0
PMID 9404727
MeSH 8-Bromo Cyclic Adenosine Monophosphate / pharmacology Animals Apoptosis / drug effects* Calcium / metabolism Calcium Channel Blockers / pharmacology Calcium Channels / metabolism Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Count / drug effects Cell Differentiation / drug effects Cell Survival / drug effects Cyclic AMP / pharmacology Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases / metabolism DNA Fragmentation / drug effects Microscopy, Phase-Contrast Nerve Growth Factors / pharmacology* Neurons / cytology* Neurons / drug effects Neuropeptides / pharmacology* PC12 Cells Peptide Fragments / pharmacology* Pituitary Adenylate Cyclase-Activating Polypeptide Rats
Times Cited 68
Human and Animal Cells PC-12(RCB0009)