Neuronal protection from apoptosis by pituitary adenylate cyclase-activating polypeptide.
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.
Tanaka
J
J
Department of Medicine, Shimane Medical University, Izumo, Japan.
Koshimura
K
K
Murakami
Y
Y
Sohmiya
M
M
Yanaihara
N
N
Kato
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D008858:Microscopy, Phase-Contrast; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009414:Nerve Growth Factors; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C108046:pituitary adenylate cyclase-activating-peptide (1-38), pig; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium