Characterization of cell death pathways in murine retinal neurodegeneration implicates cytochrome c release, caspase activation, and bid cleavage
Characterization of cell death pathways in murine retinal neurodegeneration implicates cytochrome c release, caspase activation, and bid cleavage
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DOI：
10.1006/mcne.2001.1036
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发表时间：
2001-10-01
影响因子：
3.5
通讯作者：
Jones, SE
中科院分区：
文献类型：
--
作者：
Jomary, C;Neal, MJ;Jones, SE
细胞凋亡被认为是不同遗传性视网膜疾病中感光细胞死亡的最终共同途径。然而，细胞凋亡包括多种分子相互作用途径，最终导致细胞死亡。为了开始剖析这些相互作用，我们研究了视网膜神经变性rd（retinal degeneration）模型中的关键参与者。通过免疫印迹分析和免疫细胞化学，我们发现，细胞色素c的释放发生在rd视网膜同时激活的促凋亡蛋白投标。活性形式的caspase-8和丝裂原活化蛋白激酶p38，这两者都能够裂解投标，检测在rd视网膜中的感光细胞死亡的高峰时间。此外，细胞死亡效应物半胱天冬酶-3的活化形式是可检测的，特别是在光感受器中与该峰值退化阶段平行。这些数据表明，在遗传性失明的rd小鼠模型中，两种主要凋亡途径的激活发生在感光细胞变性期间。
Apoptosis is considered to be the final common pathway of photoreceptor cell death in different inherited retinal diseases. However, apoptosis encompasses diverse pathways of molecular interactions culminating in cellular demise. To begin dissecting these interactions, we have investigated key participants in the rd (retinal degeneration) model of retinal neurodegeneration. By Western blot analysis and immunocytochemistry, we found that cytochrome c release occurs in rd retinas concurrently with the activation of the proapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detected in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particularly at the photoreceptors in parallel with this peak degenerative phase. These data suggest that activation of both major apoptotic pathways occurs during photoreceptor degeneration in the rd mouse model of inherited blindness.