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

Authors

  • Marlene Jimenez Del Rio PhD,

    Corresponding author
    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
    • Calle 62 #52-72, University of Antioquia, Medellin, Colombia
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  • Sonia Moreno MSc,

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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  • Gloria Garcia-Ospina MSc,

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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  • Omar Buritica MD,

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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  • Carlos S. Uribe MD,

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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  • Francisco Lopera MD,

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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  • Carlos Velez-Pardo PhD

    1. School of Medicine, Department of Internal Medicine, Neurology Service, Neuroscience Research Programme, University of Antioquia, Medellin, Colombia
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Abstract

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-κB-dependent pathway; mitochondrial dysfunction either by (2) H2O2 or (3) hydroxyl exposure and (4) increase of unfolded–protein stress. We also demonstrate that 17β-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. © 2003 Movement Disorder Society

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