Mitochondria-targeted (2-hydroxyamino-vinyl)-triphenyl-phosphonium releases NO(.) and protects mouse embryonic cells against irradiation-induced apoptosis.
Mitochondria-targeted (2-hydroxyamino-vinyl)-triphenyl-phosphonium releases NO(.) and protects mouse embryonic cells against irradiation-induced apoptosis.
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DOI：
10.1016/j.febslet.2009.04.050
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发表时间：
2009-06-18
期刊：
影响因子：
3.5
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
--
作者：
Belikova, Natalia A.;Jiang, Jianfei;Stoyanovsky, Detcho A.;Glumac, Ashley;Bayir, Huelya;Greenberger, Joel S.;Kagan, Valerian E.
受损的呼吸链产生活性氧，随后形成具有过氧化物酶活性的细胞色素 c-心磷脂复合物，这是细胞凋亡的早期事件。通过猝灭线粒体中细胞色素c-心磷脂复合物的过氧化物酶活性，一氧化氮可以发挥抗凋亡作用。因此，能够逐渐释放NO•的靶向线粒体的前药是有前途的辐射防护剂。在这里，我们证明（2-羟基氨基-乙烯基）-三苯基磷（HVTP）有效地在线粒体中积累，在线粒体过氧化物酶反应时释放NO•，保护小鼠胚胎细胞免受辐射诱导的细胞凋亡，并增加辐射后它们的克隆存活率。我们得出结论，线粒体靶向的过氧化物酶可激活的 NO 供体代表了一类新的有趣的辐射防护剂。
Generation of reactive oxygen species by damaged respiratory chain followed by the formation of cytochrome c-cardiolipin complex with peroxidase activity are early events in apoptosis. By quenching the peroxidase activity of cytochrome c-cardiolipin complexes in mitochondria, nitric oxide can exert anti-apoptotic effects. Therefore, mitochondria-targeted pro-drugs capable of gradual NO• release are promising radioprotectants. Here we demonstrate that (2-hydroxyamino-vinyl)-triphenyl-phosphonium (HVTP) 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.
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影响因子：
14.8
作者：
Kagan, VE;Tyurin, VA;Borisenko, GG
通讯作者：
Borisenko, GG
影响因子：
7.4
作者：
Tyurina, Yulia Y.;Tyurin, Vladimir A.;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.
影响因子：
4.8
作者：
Vlasova, Irina I.;Tyurin, Vladimir A.;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.
影响因子：
15
作者：
Wipf, P;Xiao, JB;Kagan, VE
通讯作者：
Kagan, VE
DOI：
10.1124/jpet.106.114769
发表时间：
2007-03-01
影响因子：
3.5
作者：
Jiang, Jianfei;Kurnikov, Igor;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.