Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis

被引：21

作者：

Del Rio, MJ ^{[1
]}

Moreno, S ^{[1
]}

Garcia-Ospina, G ^{[1
]}

Buritica, O ^{[1
]}

Uribe, CS ^{[1
]}

Lopera, F ^{[1
]}

Velez-Pardo, C ^{[1
]}

机构：

[1] Univ Antioquia, Sch Med, Dept Internal Med, Neurol Serv,Neurosci Res Programme, Medellin, Colombia

来源：

MOVEMENT DISORDERS | 2004年 / 19卷 / 03期

关键词：

apoptosis; dopamine; juvenile parkinsomism; parkin; stress;

D O I：

10.1002/mds.10670

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Mutations in parkin are implicated in the pathogenesis of autosomal recessive juvenile parkinsonism (AR-JP) disease. We show that homozygote Cys212Tyr parkin mutation in AR-JP patients renders lymphocytes sensitive to dopamine, iron and hydrogen peroxide stimuli. Indeed, dopamine-induced apoptosis by four alternative mechanisms converging on caspase-3 activation and apoptotic morphology: (1) NF-kappaB-dependent pathway; mitochondrial dysfunction either by (2) H2O2 or (3) hydroxyl exposure and (4) increase of unfolded-protein stress. We also demonstrate that 17beta-estradiol and testosterone prevent homozygote lymphocytes from oxidative stressors-evoked apoptosis. These results may contribute to understanding the relationship between genetic and environmental factors and iron in AR-JP. (C) 2004 Movement Disorder Society.

引用

页码：324 / 330

页数：7

共 40 条

[21] Mechanisms underlying ubiquitination [J].