A Manganese-Porphyrin Complex Decomposes H2O2, Inhibits Apoptosis, and Acts as a Radiation Mitigator in Vivo
A Manganese-Porphyrin Complex Decomposes H2O2, Inhibits Apoptosis, and Acts as a Radiation Mitigator in Vivo
复制标题
DOI：
10.1021/ml200142x
复制
发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
--
作者：
Stoyanovsky, Detcho A.;Huang, Zhentai;Kagan, Valerian E.
电离辐射触发线粒体过量产生H2O2，同时诱导内在凋亡，因此，在线粒体过氧化氢酶过度表达时清除H2O2增加了体外和体内的辐射抗性。作为基因治疗的替代方案，我们测试了Mn-(III)-卟啉复合物清除线粒体H2O2的潜力。我们报道了三苯基[(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]磷- mn -(III)优先区隔进入小鼠胚胎细胞线粒体，与H2O2反应，阻碍γ射线诱导的线粒体凋亡，并提高小鼠在全身γ射线照射下的存活率。
Ionizing radiation triggers mitochondria] overproduction of H2O2 with concomitant induction of intrinsic apoptosis, whereby clearance of H2O2 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 H2O2. 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 H2O2, impedes gamma-ray-induced mitochondrial apoptosis, and increases the survival of mice exposed to whole body irradiation with gamma-rays.