Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis.

Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis.
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遗传编码的氧化还原传感器鉴定了ROS在退化性和线粒体疾病发病机理中的作用。

DOI:
10.1016/j.nbd.2011.08.022
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发表时间:
2012-01
影响因子:
6.1
通讯作者:
Palladino, Michael J.
Palladino, Michael J.
中科院分区:
医学1区
文献类型:
--
作者:
Liu, Zhaohui;Celotto, Alicia M.;Romero, Guillermo;Wipf, Peter;Palladino, Michael J.

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线粒体功能障碍在神经退行性疾病、许多其他疾病状态和衰老的发病机制中起重要作用。在动物模型系统中监测组织内和随时间推移的活性氧(ROS)的能力具有重要的研究价值。最近,氧化还原敏感的荧光蛋白已被开发。表达靶向线粒体的遗传编码的氧化还原敏感性GFP(roGFP)的转基因果蝇用作线粒体功能障碍和ROS的有用的体内测定。我们已经产生了转基因苍蝇表达的脑靶向roGFP 2,证明了其在培养细胞和体内氧化还原变化的反应,并利用这种蛋白质发现升高的ROS作为一个贡献者的发病机制,在一个特征性的神经变性突变体和线粒体脑肌病模型。这些研究确定了ROS在与线粒体疾病相关的发病机制中的作用,并证明了果蝇中遗传编码的氧化还原传感器的实用性。
Mitochondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases, numerous other disease states and senescence. The ability to monitor reactive oxygen species (ROS) within tissues and over time in animal model systems is of significant research value. Recently, redox-sensitive fluorescent proteins have been developed. Transgenic flies expressing genetically encoded redox-sensitive GFPs (roGFPs) targeted to the mitochondria function as a useful in vivo assay of mitochondrial dysfunction and ROS. We have generated transgenic flies expressing a mitochondrial-targeted roGFP2, demonstrated its responsiveness to redox changes in cultured cells and in vivo and utilized this protein to discover elevated ROS as a contributor to pathogenesis in a characterized neurodegeneration mutant and in a model of mitochondrial encephalomyopathy. These studies identify the role of ROS in pathogenesis associated with mitochondrial disease and demonstrate the utility of genetically encoded redox sensors in Drosophila.
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