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

被引：47

作者：

Onoue, S ^{[1
]}

Ohshima, K

Endo, K

Yajima, T

Kashimoto, K

机构：

[1] Itoham Foods Inc, Div Hlth Sci, Moriya, Ibaraki 3020104, Japan

[2] Toho Univ, Sch Pharmaceut Sci, Funabashi, Chiba 2748510, Japan

[3] Natl Canc Ctr, Res Inst, Div Growth Factor, Tokyo 104, Japan

来源：

FEBS LETTERS | 2002年 / 522卷 / 1-3期

关键词：

pituitary adenylate cyclase-activating polypeptide; vasoactive intestinal peptide; PC12; cell; prion protein-106-126; caspase; circular dichroism;

D O I：

10.1016/S0014-5793(02)02886-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (106126)]. Concomitant application of neuropeptide with PrP(106126) (5 X 10(-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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：65 / 70

页数：6

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