Stoyanovsky Detcho A, Huang Zhentai, Jiang Jianfei, Belikova Natalia A, Tyurin Vladimir, Epperly Michael W, Greenberger Joel S, Bayir Hülya, Kagan Valerian E
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA.
ACS Med Chem Lett. 2011 Nov 10;2(11):814-817. doi: 10.1021/ml200142x.
Ionizing radiation triggers mitochondrial overproduction of H(2)O(2) with concomitant induction of intrinsic apoptosis, whereby clearance of H(2)O(2) upon overexpression of mitochondrial catalase increases radioresistance in vitro and in vivo. As an alternative to gene therapy, we tested the potential of Mn((III))-porphyrin complexes to clear mitochondrial H(2)O(2). We report that triphenyl-[(2E)-2-[4-[(1Z,4Z,9Z,15Z)-10,15,20-tris(4-aminophenyl)-21,23-dihydroporphyrin-5-yl]phenyl]iminoethyl]phosphonium-Mn((III)) compartmentalizes preferentially into mitochondria of mouse embryonic cells, reacts with H(2)O(2), impedes γ-ray-induced mitochondrial apoptosis, and increases the survival of mice exposed to whole body irradiation with γ-rays.
电离辐射引发线粒体过量产生H₂O₂，并伴随诱导内源性凋亡，而线粒体过氧化氢酶过表达时清除H₂O₂可在体外和体内增加放射抗性。作为基因治疗的替代方法，我们测试了锰（III）-卟啉配合物清除线粒体H₂O₂的潜力。我们报告称，三苯基-[(2E)-2-[4-[(1Z,4Z,9Z,15Z)-10,15,20-三(4-氨基苯基)-21,23-二氢卟啉-5-基]苯基]亚氨基乙基]鏻-锰（III）优先定位于小鼠胚胎细胞的线粒体中，与H₂O₂反应，阻碍γ射线诱导的线粒体凋亡，并提高接受全身γ射线照射小鼠的存活率。
