Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Mol Nutr Food Res. 2013 Aug;57(8):1410-22. doi: 10.1002/mnfr.201200801. Epub 2013 May 3.
Rotenone is a toxicant believed to contribute to the development of Parkinson's disease.
Using human peripheral blood lymphocytes we demonstrated that exposure to rotenone resulted in disruption of electron transport accompanied by the production of reactive oxygen species, development of apoptosis and elevation of peroxidase activity of mitochondria. Employing LC/MS-based lipidomics/oxidative lipidomics we characterized molecular species of cardiolipin (CL) and its oxidation/hydrolysis products formed early in apoptosis and associated with the rotenone-induced mitochondrial dysfunction.
The major oxidized CL species - tetra-linoleoyl-CL - underwent oxidation to yield epoxy-C18:2 and dihydroxy-C18:2 derivatives predominantly localized in sn-1 and sn-2 positions, respectively. In addition, accumulation of mono-lyso-CL species and oxygenated free C18:2 were detected in rotenone-treated lymphocytes. These oxidation/hydrolysis products may be useful for the development of new biomarkers of mitochondrial dysfunction.
鱼藤酮是一种被认为会导致帕金森病发展的有毒物质。
使用人外周血淋巴细胞，我们证明暴露于鱼藤酮会导致电子传递中断，伴随着活性氧的产生、细胞凋亡的发展和线粒体过氧化物酶活性的升高。通过基于 LC/MS 的脂质组学/氧化脂质组学，我们对早期凋亡中形成的并与鱼藤酮诱导的线粒体功能障碍相关的 cardiolipin (CL)及其氧化/水解产物的分子种类进行了表征。
主要氧化的 CL 种类——四亚油酰基-CL——发生氧化，生成环氧-C18:2 和二羟基-C18:2 衍生物，主要分别定位于 sn-1 和 sn-2 位置。此外，在鱼藤酮处理的淋巴细胞中还检测到单溶血 CL 种类和含氧游离 C18:2 的积累。这些氧化/水解产物可能有助于开发线粒体功能障碍的新生物标志物。
