Glutathione Peroxidase 4 Is Required for Maturation of Photoreceptor Cells
Glutathione Peroxidase 4 Is Required for Maturation of Photoreceptor Cells
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DOI：
10.1074/jbc.m111.335174
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发表时间：
2012-03-02
影响因子：
4.8
通讯作者：
Yanagi, Yasuo
中科院分区：
文献类型：
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作者：
Ueta, Takashi;Inoue, Tatsuya;Yanagi, Yasuo
氧化应激与感光细胞的病理有关，并且抗氧化酶对感光细胞的保护作用已被充分了解。然而，它们的重要性仍然未知。在这项研究中，我们培育了光感受器特异性谷胱甘肽过氧化物酶 4 (GPx4) 条件敲除 (CKO) 小鼠，并展示了 GPx4 对光感受器细胞的关键作用。在野生型视网膜中，主要的 GPx4 表达位于线粒体中，表明线粒体变体是视网膜中主要的 GPx4。在 GPx4-CKO 小鼠中，尽管感光细胞在 P12 时发育并分化为视杆细胞和视锥细胞，但在 P21 时它们迅速发生剧烈退化并完全消失。 GPx4-CKO 小鼠的感光细胞死亡与凋亡诱导因子 (AIF) 和 TUNEL 阳性细胞的核转位有关。经历凋亡之前的感光细胞（P11）表现出线粒体生物量减少、连接纤毛数量减少以及外部节段结构紊乱。这些发现表明 GPx4 是感光细胞成熟和存活的关键抗氧化酶。
Oxidative stress is implicated in the pathologies of photoreceptor cells, and the protective role of antioxidant enzymes for photoreceptor cells have been well understood. However, their essentiality has remained unknown. In this study we generated photoreceptor-specific conditional knock-out (CKO) mice of glutathione peroxidase 4 (GPx4) and showed the critical role of GPx4 for photoreceptor cells. In the wild-type retina the dominant GPx4 expression was in the mitochondria, indicating the mitochondrial variant was the major GPx4 in the retina. In the GPx4-CKO mice, although photoreceptor cells developed and differentiated into rod and cone cells by P12, they rapidly underwent drastic degeneration and completely disappeared by P21. The photoreceptor cell death in the GPx4-CKO mice was associated with the nuclear translocation of apoptosis-inducing factor (AIF) and TUNEL-positive cells. Photoreceptor cells before undergoing apoptosis (P11) exhibited decreased mitochondrial biomass, decreased number of connecting cilia, as well as disorganized structure of outer segments. These findings indicate that GPx4 is a critical antioxidant enzyme for the maturation and survival of photoreceptor cells.