The neuropeptide PACAP attenuates beta-amyloid (1-42)-induced toxicity in PC12 cells.
Pituitary adenylate cyclase activating polypeptide (PACAP) modulates neurotransmission in the central and peripheral nervous systems. In vitro and in vivo studies have shown the protective effects of PACAP against neuronal damage induced by ischemia and agonists of NMDA-type glutamate receptors. Here, we demonstrated that PACAP also protected against neuronal toxicity induced by beta-amyloid (Abeta) peptide, aggregation of which is a causative factor for Alzheimer's disease. PACAP (10(-9)M) rescued 80% of decreased cell viability and 50% of elevated caspase-3 activity that resulted from exposure of PC12 cells to Abeta. PACAP was at least 10(4)-fold more effective than other neuropeptides including vasoactive intestinal peptide (VIP) and humanin, which correlated with the level of cAMP accumulation. Thus, our results suggested that PACAP attenuates Abeta-induced cell death in PC12 cells through an increase in cAMP and that caspase-3 deactivation by PACAP is involved in the signaling pathway for this neuroprotection.
Onoue
Satomi
S
Health Science Division, Central Research Institute Itoham Foods Inc., 1-2-1 Kubogaoka, Moriya, Ibaraki 302-0104, Japan. onoue@fureai.or.jp
Endo
Kosuke
K
Ohshima
Keiichi
K
Yajima
Takehiko
T
Kashimoto
Kazuhisa
K
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis / Q000235:genetics; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics
C495403:Adcyap1 protein, rat; D016229:Amyloid beta-Peptides; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; C075222:amyloid beta-protein (1-42); D000242:Cyclic AMP; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases