Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria.
Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria.
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DOI：
10.1016/j.freeradbiomed.2009.05.012
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发表时间：
2009-08-01
影响因子：
7.4
通讯作者：
Richardson, Arlan
中科院分区：
文献类型：
--
作者：
Liang, Hanyu;Ran, Qitao;Jang, Youngmok Charles;Holstein, Deborah;Lechleiter, James;McDonald-Marsh, Tiffany;Musatov, Andrej;Song, Wook;Van Remmen, Holly;Richardson, Arlan
关键词：
谷胱甘肽过氧化物酶4（Gpx 4）是一种独特的抗氧化酶，可以修复生物膜的氧化损伤。在本研究中，我们使用过表达Gpx 4 [Tg（GPX 4 +/0）]的转基因小鼠和Gpx 4缺陷小鼠（Gpx 4 +/−小鼠）检测了Gpx 4对线粒体释放各种致突变蛋白的影响。敌草快暴露引发细胞凋亡，通过内源性途径发生，并导致线粒体释放细胞色素c（cyt。c）野生型（Wt）小鼠肝脏中的Smac/DIABLO和Omi/HtrA 2。肝细胞凋亡与细胞色素。c释放在Tg（GPX 4 +/0）小鼠中受到抑制，但在Gpx 4 +/−小鼠中加剧;然而，Tg（GPX 4 +/0）和Gpx 4 +/−小鼠都没有显示线粒体释放的Smac/DIABLO或Omi/HtrA 2水平的任何改变。Smac/DIABLO和Omi/HtrA 2主要存在于细胞膜间隙和基质中，而cyt. c和Gpx 4均与内膜结合。此外，敌草快暴露诱导Wt小鼠肝脏中的心磷脂过氧化; Tg（GPX 4 +/0）小鼠的心磷脂过氧化水平降低，但Gpx 4 +/−小鼠升高。这些数据表明，Gpx 4差异调节致炎蛋白的释放，由于其在线粒体内膜的位置和修复心磷脂过氧化的能力。
Glutathione peroxidase 4 (Gpx4) is a unique antioxidant enzyme that repairs oxidative damage to biomembranes. In the present study, we examined the effect of Gpx4 on the release of various apoptogenic proteins from mitochondria using transgenic mice overexpressing Gpx4 [Tg(GPX4+/0)] and mice deficient in Gpx4 (Gpx4+/− mice). Diquat exposure triggered apoptosis that occurred through intrinsic pathway and resulted in the mitochondrial release of cytochrome c (cyt. c), Smac/DIABLO, and Omi/HtrA2 in the liver of wild-type (Wt) mice. Liver apoptosis and cyt. c release were suppressed in Tg(GPX4+/0) mice but exacerbated in Gpx4+/− mice; however, neither the Tg(GPX4+/0) nor the Gpx4+/− mice showed any alterations in the levels of Smac/DIABLO or Omi/HtrA2 released from mitochondria. Submitochondrial fractionation data showed that Smac/DIABLO and Omi/HtrA2 existed primarily in the intermembrane space and matrix, while cyt. c and Gpx4 were both associated with inner membrane. In addition, diquat exposure induced cardiolipin peroxidation in the liver of Wt mice; the levels of cardiolipin peroxidation were reduced in Tg(GPX4+/0) mice but elevated in Gpx4+/− mice. These data suggest that Gpx4 differentially regulates apoptogenic protein release due to its inner membrane location in mitochondria and its ability to repair cardiolipin peroxidation.
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DOI：
10.1083/jcb.93.1.97
发表时间：
1982-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujiki Y;Hubbard AL;Fowler S;Lazarow PB
通讯作者：
Lazarow PB
影响因子：
14.8
作者：
Kagan, VE;Tyurin, VA;Borisenko, GG
通讯作者：
Borisenko, GG
影响因子：
3.5
作者：
Choo, YS;Johnson, GVW;Lesort, M
通讯作者：
Lesort, M
DOI：
10.1073/pnas.90.17.7951
发表时间：
1993-09-01
影响因子：
11.1
作者：
LOO, DT;COPANI, A;COTMAN, CW
通讯作者：
COTMAN, CW
影响因子：
3.9
作者：
Kriska, T;Korytowski, W;Girotti, AW
通讯作者：
Girotti, AW