Stoyanovsky Detcho A, Jiang Jianfei, Murphy Michael P, Epperly Michael, Zhang Xiaolan, Li Song, Greenberger Joel, Kagan Valerian, Bayır Hülya
Departments of Environmental and Occupational Health, Critical Care Medicine, Radiation Oncology, and Pharmaceutical Sciences, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
Medical Research Council Mitochondrial Biology Unit , Wellcome Trust/MRC Building, Hills Road, Cambridge, U.K.
ACS Med Chem Lett. 2014 Nov 18;5(12):1304-1307. doi: 10.1021/ml5003635. eCollection 2014 Dec 11.
Ionizing radiation (IR) triggers mitochondrial overproduction of HO and accumulation of lipid hydroperoxides leading to the induction of apoptotic and necroptotic cell death pathways. Given the high catalytic efficiency of the seleno-enzyme glutathione peroxidase (Gpx) toward reduction of lipid hydroperoxides and HO, we tested the potential of mitochondria-targeted derivatives of ebselen to mitigate the deleterious effects of IR. We report that 2-[[2-[4-(3-oxo-1,2-benzoselenazol-2-yl)phenyl]acetyl]amino]ethyl-triphenyl-phosphonium chloride (MitoPeroxidase 2) was effective in reducing lipid hydroperoxides, preventing apoptotic cell death, and, when administered 24 h postirradiation, increased the survival of mice exposed to whole body γ-irradiation.
电离辐射（IR）会引发线粒体中羟基自由基（HO）的过量产生以及脂质氢过氧化物的积累，从而导致凋亡和坏死性细胞死亡途径的诱导。鉴于硒酶谷胱甘肽过氧化物酶（Gpx）对脂质氢过氧化物和HO还原具有较高的催化效率，我们测试了线粒体靶向的依布硒啉衍生物减轻IR有害影响的潜力。我们报告称，2-[[2-[4-(3-氧代-1,2-苯并硒唑-2-基)苯基]乙酰基]氨基]乙基三苯基氯化膦（线粒体过氧化物酶2）在减少脂质氢过氧化物、防止凋亡性细胞死亡方面有效，并且在照射后24小时给药时，可提高全身γ照射小鼠的存活率。
