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Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis.
- Source :
-
Movement Disorders . Mar2004, Vol. 19 Issue 3, p324-330. 7p. - Publication Year :
- 2004
-
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 unfoldedprotein 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 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08853185
- Volume :
- 19
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Movement Disorders
- Publication Type :
- Academic Journal
- Accession number :
- 12554687
- Full Text :
- https://doi.org/10.1002/mds.10670