title: A manganese-porphyrin complex decomposes H(2)O(2), inhibits apoptosis, and acts as a radiation mitigator in vivo.
abstract: 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.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Detcho A
authors.initials: DA
authors.lastname: Stoyanovsky
authors.forename: Zhentai
authors.initials: Z
authors.lastname: Huang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Jiang
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Belikova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tyurin
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan