α-Synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3

被引：34

作者：

Adamczyk, Agata ^{[1
]}

Kazmierczak, Anna ^{[1
]}

Czapski, Grzegorz Arkadiusz ^{[1
]}

Strosznajder, Joanna Benigna ^{[1
]}

机构：

[1] Polish Acad Sci, Dept Cellular Signaling, Mossakowski Med Res Ctr, PL-02106 Warsaw, Poland

来源：

FEBS LETTERS | 2010年 / 584卷 / 15期

关键词：

alpha-Synuclein; Nitric oxide; Caspase-3; Poly(ADP-ribose) polymerase-1; HT22; cell; PARKINSONS-DISEASE; INDUCED APOPTOSIS; MITOCHONDRIAL DYSFUNCTION; NEUROBLASTOMA-CELLS; S-NITROSYLATION; SYNTHASE; ENDOCYTOSIS; EXPRESSION; NEURONS; MODEL;

D O I：

10.1016/j.febslet.2010.07.019

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：

Our previous studies indicated that exogenous alpha-synuclein (ASN) activates neuronal nitric oxide (NO) synthase (nNOS) in rat brain slices. The present study, carried out on immortalized hippocampal neuronal cells (HT22), was designed to extend the previous results by showing the molecular pathway of NO-mediated cell death induced by exogenous ASN. Extracellular ASN (10 mu M) was found to stimulate nitric oxide synthase (NOS) and increase caspase-3 activity in HT22 cells, leading to poly(ADP-ribose) polymerase (PARP-1) cleavage. The inhibitor of Ca(2+)-dependent NOS (N-nitro-L-arginine, 100 mu M) prevented ASN-evoked caspase-3 activation and PARP-1 degradation. ASN exposure resulted in apoptotic death of HT22 cells and this effect was reversed by inhibition of NO synthesis and caspase-3 activity. Our results demonstrated that extracellular ASN induces neuronal cell death by NO-mediated caspase-3 activation. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：3504 / 3508

页数：5

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