摘要
视网膜炎色点作为神经病变疾病中的一种,其细胞凋亡的分子机制尚未研究清楚.笔者讨论了来自线粒体与来自内质网的两种细胞凋亡途径在rd1模型大鼠视网膜色点发生的病变过程中共同作用.在体内以及体外细胞模型中,AIF和caspase-12都转移到死亡的光感受器细胞的细胞核上,并且这两种凋亡因子的转移都受到胞内钙离子动态平衡以及钙蛋白酶的活性改变的影响.基因表达下调等试验证明了AIF在该凋亡过程中起主要作用,而caspase-12起到加强的效果,从而说明了在发生病变的神经元中的线粒体和内质网中两个caspase依赖性的凋亡途径之间的关系.对这些问题的进一步研究有助于对细胞凋亡分子机制的深入认识并促进该疾病治疗研究的发展.
Molecular mechanisms underlying apoptosis in retinitis pigrnentosa, as in other neurodegenerative diseases, are still elusive. Two apoptotic pathways, one from the mitochondrion and one from the endoplasmic reticulum, are coactivated during the degenerative process in an animal model of retinitis pigmentosa, the rdl mouse. Both AIF and caspase - 12 are verified to translocate to the nucleus of dying photoreceptors in vivo and in an in vitro cellular model. Translocation of both apoptotic factom depends on changes in intracellular calcium homeostasis and on calpain activity. Knockdown experiments defined that AIF plays the major role in this apoptotic event, whereas caspase -12 has a reinforcing effect. This provides a link between two executor caspase - independent apoptotic pathways involving mitochondrion and endoplasmic reticulum in a degenerating neuron. The further studies of these problems help to understand the apoptotic molecular mechanisms and increase the development of a cure for this blinding disease.
