RESUMEN
Complex I activity is reduced in cytoplasmic hybrid (cybrid) cell lines that contain mitochondrial DNA (mtDNA) from sporadic Parkinson's disease (PD) patients. This implies that mtDNA aberration occurs in sporadic PD. To assess the integrity of mtDNA in autosomal dominant PD arising from mutation of the alpha-synuclein gene, we transferred mitochondrial genes from PD-affected members of the Italian-American Contursi kindred to cells previously depleted of their endogenous mtDNA. Unlike cybrid cell lines expressing mtDNA from persons with sporadic or maternally inherited PD, the resultant Contursi cybrid lines did not manifest complex I deficiency, indicating that in Contursi PD mtDNA integrity is relatively preserved. Compared to control cybrids, however, Contursi cybrid lines did show some evidence of oxidative stress. For reasons that are unclear, at least a limited amount of mtDNA damage may nevertheless develop in PD patients with alpha-synuclein mutation.
Asunto(s)
ADN Mitocondrial/genética , NADH NADPH Oxidorreductasas/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Plaquetas/metabolismo , Plaquetas/ultraestructura , Catalasa/metabolismo , ADN Mitocondrial/sangre , Transporte de Electrón , Complejo I de Transporte de Electrón , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Genes Dominantes , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Células Híbridas/metabolismo , Masculino , Persona de Mediana Edad , NADH NADPH Oxidorreductasas/metabolismo , Neuroblastoma , Valores de Referencia , Células Tumorales CultivadasRESUMEN
Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder of unknown etiology. We hypothesized that mitochondrial DNA (mtDNA) aberration could occur in this disease and contribute to its pathogenesis. To address this we created transmitochondrial cytoplasmic hybrid (cybrid) cell lines expressing mitochondrial genes from persons with PSP. The presence of cybrid mtDNA aberration was screened for by biochemical assay of mitochondrial gene products. Relative to a control cybrid set, complex I activity was reduced in PSP cybrid lines (p<0.005). Antioxidant enzyme activities were elevated in PSP cybrid lines. These data suggest that mtDNA aberration occurs in PSP, causes electron transport chain pathology, and can produce oxidative stress. Further study of mitochondrial dysfunction in PSP may yield insights into why neurodegeneration occurs in this disease.