Mitochondria-targeted (2-hydroxyamino-vinyl)-triphenyl-phosphonium releases NO and protects mouse embryonic cells against irradiation-induced apoptosis

Abstract

AbstractGeneration of reactive oxygen species by damaged respiratory chain followed by the formation of cytochrome c (cyt c)–cardiolipin (CL) complex with peroxidase activity are early events in apoptosis. By quenching the peroxidase activity of cyt c–CL complexes in mitochondria, nitric oxide can exert anti-apoptotic effects. Therefore, mitochondria-targeted pro-drugs capable of gradual nitric oxide radical (NO) release are promising radioprotectants. Here we demonstrate that (2-hydroxyamino-vinyl)-triphenyl-phosphonium effectively accumulates in mitochondria, releases NO upon mitochondrial peroxidase reaction, protects mouse embryonic cells from irradiation-induced apoptosis and increases their clonogenic survival after irradiation. We conclude that mitochondria-targeted peroxidase-activatable NO-donors represent a new interesting class of radioprotectors