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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Relationships among molecular genetic and respiratory properties of Parkinson's disease cybrid cells show similarities to Parkinson's brain tissues.
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Relationships among molecular genetic and respiratory properties of Parkinson's disease cybrid cells show similarities to Parkinson's brain tissues.

机译：帕金森氏病混合细胞的分子遗传学和呼吸特性之间的关系显示出与帕金森氏脑组织的相似性。

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摘要

We have studied sporadic Parkinson's disease (sPD) from expression of patient mitochondrial DNA (mtDNA) in neural cells devoid of their own mtDNA, the "cybrid" model. In spite of reproducing several properties of sPD brain, it remains unclear whether sPD cybrid cells reflect more complex sPD brain bioenergetic pathophysiology. We characterized and correlated respiration of intact sPD cybrid cells with electron transport chain (ETC) protein assembly, complex I ETC gene expression and ETC protein levels in sPD brain. We also assayed expression for multiple ETC genes coded by mtDNA and nuclear DNA (nDNA) in sPD cybrid cells and brain. sPD cybrid cells have reduced levels of mtDNA genes, variable compensatory normalization of mitochondrial gene expression and show robust correlations with mitochondrial ETC gene expression in sPD brains. Relationships among ETC protein levels predict impaired complex I-mediated respiration in sPD brain. That sPD cybrid cells and sPD brain samples show very correlated regulation of nDNA and mtDNA ETC transcriptomes suggests similar bioenergetic physiologies. We propose that further insights into sPD pathogenesis will follow elucidation of mechanisms leading to reduced mtDNA gene levels in sPD cybrids. This will require characterization of the abnormalities and dynamics of mtDNA changes propagated through sPD cybrids over time.
机译：我们已经从患者线粒体DNA（mtDNA）在缺乏自身mtDNA（即“杂交”模型）的神经细胞中表达研究了散发性帕金森氏病（sPD）。尽管重现了sPD脑的几种特性，但尚不清楚sPD混合细胞是否反映了更复杂的sPD脑生物能病理生理学。我们表征和关联完整的sPD cybrid细胞的呼吸与电子运输链（ETC）蛋白质组装，复杂I ETC基因表达和sPD脑中的ETC蛋白质水平。我们还分析了sPD杂交细胞和大脑中由mtDNA和核DNA（nDNA）编码的多个ETC基因的表达。 sPD杂交细胞的mtDNA基因水平降低，线粒体基因表达的可变补偿归一化，并且与sPD大脑中的线粒体ETC基因表达呈显着相关性。 ETC蛋白水平之间的关系预测sPD大脑中复杂的I介导的呼吸功能受损。 sPD混合细胞和sPD脑样本显示出对nDNA和mtDNA ETC转录组的调节非常相关，表明了类似的生物能生理学。我们建议对sPD发病机制的进一步了解将在阐明导致sPD杂交群中mtDNA基因水平降低的机制之后。这将需要表征通过sPD杂交体随时间传播的mtDNA变化的异常和动态。

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