Decreased expression of pro-apoptotic Bcl-2 family members during retinal development and differential sensitivity to cell death
Decreased expression of pro-apoptotic Bcl-2 family members during retinal development and differential sensitivity to cell death
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DOI：
10.1016/j.ydbio.2005.12.026
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发表时间：
2006-03-01
影响因子：
2.7
通讯作者：
Cotter, TG
中科院分区：
文献类型：
--
作者：
Donovan, M;Doonan, F;Cotter, TG
细胞凋亡在哺乳动物视网膜发育过程中起着至关重要的作用。然而，一旦视网膜完全分化，重点必须转移到生存和机制必须到位，以防止不适当的细胞死亡。在本研究中，我们确定了线粒体通透性水平的潜在控制点。我们发现，已知参与视网膜通透性转换和生理性细胞死亡调节的促凋亡Bcl-2家族成员在出生后视网膜发育过程中下调。此外，我们还证明了对已知靶向线粒体的各种刺激诱导的视网膜细胞死亡的年龄依赖性易感性。这些结果可能解释了为什么视网膜细胞根据其发育阶段采用不同的死亡途径。与发育性凋亡相反，在一些动物模型中，病理性视网膜细胞死亡的发生已被报道为与caspase激活无关。在这里，我们表明，不仅细胞色素c的释放被排除在退化的视网膜之外，而且其他促死亡分子如Omi/HtrA 2和AIF也保留在视网膜中。我们的结果表明视网膜发育过程中“死亡基因”（如促凋亡Bcl-2家族成员）的转录调节通过阻止原型线粒体死亡途径的执行而在成年有丝分裂后神经元中提供保护。(c)2005年爱思唯尔公司All rights reserved.
Apoptosis plays a crucial role in the sculpture of the mammalian retina during development. However, once the retina is fully differentiated, the emphasis must shift towards survival and mechanisms have to be put in place to prevent inappropriate cell death. In this study, we identify a potential control point at the level of mitochondrial permeability. We show that pro-apoptotic Bcl-2 family members known to be involved in the regulation of permeability transition and physiological cell death in the retina are down regulated during postnatal retinal development. In addition, we demonstrate an age-dependent susceptibility to retinal cell death induced by various stimuli known to target mitochondrion. These results potentially explain why retinal cells employ different death pathways depending on their stage of development. In contrast to developmental apoptosis, pathological retinal cell death in several animal models has been reported to occur independently of caspase activation. Here, we show that not only is cytochrome c release precluded from degenerating retinas but other pro-death molecules Such as Omi/HtrA2 and AIF also remain in the mitochondrion. Our results indicate that transcriptional regulation of 'death genes' such as pro-apoptotic Bcl-2 family members during retinal development affords protection in adult post-mitotic neurons by preventing execution of the archetypal mitochondrial death pathway. (c) 2005 Elsevier Inc. All rights reserved.