Afferent regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus.
Afferent regulation of cytochrome-c and active caspase-9 in the avian cochlear nucleus.
复制标题
鸟类耳蜗核中细胞色素-c 和活性 caspase-9 的传入调节。
DOI：
10.1016/s0306-4522(03)00387-7
复制
发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Hyson,RL
中科院分区：
文献类型：
--
作者：
Wilkinson,BL;Elam,JS;Fadool,DA;Hyson,RL
在发育过程中，一个亚群（约30%）的神经元在鸟类耳蜗核，核大细胞（NM），死亡后，耳蜗。很明显，来自听神经的神经元活动提供了对NM中细胞存活至关重要的营养支持。调节细胞凋亡的细胞内信号级联的几个方面已经被定义为神经元中自然发生的或程序性细胞死亡。这些细胞内级联涉及细胞色素c从线粒体挤出到胞质溶胶中以及随后的蛋白水解半胱天冬酶级联的激活，其最终作用于导致细胞死亡的底物。相反，负责去传入神经诱导的细胞死亡的细胞内信号级联并不完全清楚。在本系列的实验中，潜在的挤压细胞色素-C从线粒体进入胞质溶胶，和半胱氨酸天冬氨酸蛋白酶的激活进行了检查，在NM后deafferentation。细胞色素C免疫反应性增加6小时内deafferentation后，并持续至少3-5天手术后。然而，细胞色素-C是无法检测到的免疫沉淀物从去传入NM神经元的胞质组分。这表明细胞色素c的免疫反应性增加与线粒体增殖有关。作为阳性对照，在用红藻氨酸处理的去传入NM神经元的胞质级分中检测到细胞色素-c，红藻氨酸是一种已知引起细胞色素-c释放到胞质中的物质。此外，免疫反应性下游活性caspase-9增加后，耳蜗消融。这种增加在耳蜗移除后3小时内观察到，但在手术后4天没有观察到，这是NM神经元的死亡群体已经退化后的时间点。总之，这些研究结果表明，去传入NM神经元的结果半胱天冬酶激活，但这种激活可能是细胞色素C的独立。
During development, a subpopulation (approximately 30%) of neurons in the avian cochlear nucleus, nucleus magnocellularis (NM), dies following removal of the cochlea. It is clear that neuronal activity coming from the auditory nerve provides trophic support critical for cell survival in the NM. Several aspects of the intracellular signaling cascades that regulate apoptosis have been defined for naturally occurring, or programmed cell death, in neurons. These intracellular cascades involve the extrusion of cytochrome-c from the mitochondria into the cytosol and the subsequent activation of proteolytic caspase cascades, which ultimately act on substrates that lead to the death of the cell. In contrast, the intracellular signaling cascades responsible for deafferentation-induced cell death are not fully understood. In the present series of experiments, the potential extrusion of cytochrome-c from the mitochondria into the cytosol, and the activation of caspases were examined in the NM following deafferentation. Cytochrome-c immunoreactivity increased within 6 h following deafferentation and persisted for at least 3–5 days following surgery. However, cytochrome-c was not detectable within immunoprecipitates obtained from cytosolic fractions of deafferented NM neurons. This suggests that the increased immunoreactivity of cytochrome-c is related to mitochondrial proliferation. As a positive control, cytochrome-c was detected in cytosolic fractions of deafferented NM neurons treated with kainic acid, a substance known to cause cytochrome-c release into the cytosol. In addition, immunoreactivity for downstream active caspase-9 did increase following cochlea ablation. This increase was observed within 3 h following cochlea removal, but was not observed 4 days following surgery, a time point after the dying population of NM neurons have already degenerated. Together, these findings suggest that deafferentation of NM neurons results in caspase activation, but this activation may be cytochrome-c independent.