RRC ID 41652
Author Onoue S, Endo K, Ohshima K, Yajima T, Kashimoto K.
Title The neuropeptide PACAP attenuates beta-amyloid (1-42)-induced toxicity in PC12 cells.
Journal Peptides
Abstract 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.
Volume 23(8)
Pages 1471-8
Published 2002-8-1
DOI 10.1016/s0196-9781(02)00085-2
PII S0196978102000852
PMID 12182949
MeSH Amyloid beta-Peptides / toxicity* Animals Caspase 3 Caspases / metabolism Cyclic AMP / metabolism Neuropeptides / metabolism* PC12 Cells Peptide Fragments / toxicity* Pituitary Adenylate Cyclase-Activating Polypeptide RNA, Messenger / metabolism Rats Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide Receptors, Pituitary Hormone / biosynthesis Receptors, Pituitary Hormone / genetics Receptors, Vasoactive Intestinal Peptide / biosynthesis Receptors, Vasoactive Intestinal Peptide / genetics
IF 2.843
Times Cited 89
WOS Category PHARMACOLOGY & PHARMACY ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells