PACAP protects neuronal PC12 cells from the cytotoxicity of human prion protein fragment 106-126.

Abstract:

:Misfolding of the prion protein yields amyloidogenic isoforms, and it shows exacerbating neuronal damage in neurodegenerative disorders including prion diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) potently stimulate neuritogenesis and survival of neuronal cells in the central nervous system. Here, we tested these neuropeptides on neurotoxicity in PC12 cells induced by the prion protein fragment 106-126 [PrP (106-126)]. Concomitant application of neuropeptide with PrP(106-126) (5x10(-5) M) inhibited the delayed death of neuron-like PC12 cells. In particular, PACAP27 inhibited the neurotoxicity of PrP(106-126) at low concentrations (>10(-15) M), characterized by the deactivation of PrP(106-126)-stimulated caspase-3. The neuroprotective effect of PACAP27 was antagonized by the selective PKA inhibitor, H89, or the MAP kinase inhibitor, U0126. These results suggest that PACAP27 attenuates PrP(106-126)-induced delayed neurotoxicity in PC12 cells by activating both PKA and MAP kinases mediated by PAC1 receptor.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Onoue S,Ohshima K,Endo K,Yajima T,Kashimoto K

doi

10.1016/s0014-5793(02)02886-7

keywords:

subject

Has Abstract

pub_date

2002-07-03 00:00:00

pages

65-70

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302028867

journal_volume

522

pub_type

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