Caspase-9:: Involvement in secondary death of axotomized rat retinal ganglion cells in vivo
Caspase-9:: Involvement in secondary death of axotomized rat retinal ganglion cells in vivo
复制标题
DOI：
10.1016/s0169-328x(00)00256-4
复制
发表时间：
2000-12-28
期刊：
影响因子：
--
通讯作者：
Bähr, M
中科院分区：
文献类型：
--
作者：
Kermer, P;Ankerhold, R;Bähr, M
最近，我们发现成年大鼠视网膜神经节细胞(RGC)在视神经切断后通过激活caspase-3而死亡。在本研究中，我们报道了免疫印迹分析和蛋白酶活性测定表明，caspase-9是caspase-3的重要激活物，在成年大鼠视网膜轴突切断后被激活。通过重复眼内注射特定的抑制剂降低caspase-9的活性，显著防止了RGC的死亡。Caspase-9活性可被抑制剂处理和应用IGF-I和BDNF有效地阻断，这两种神经营养因子已被证明在该模型中具有高度的神经保护作用。综上所述，我们的数据表明，caspase-9在体内视网膜节细胞的凋亡诱导中起关键作用，并受生长和生存因子的调节。因此，对创伤后神经元死亡和存活的潜在机制提供更多的洞察可能成为改进未来预防或至少减少神经元损伤的严重后果的治疗策略的基础。(C)2000年爱思唯尔科学公司。版权所有。
Recently we have shown that adult rat retinal ganglion cells (RGCs) die by apoptosis following optic nerve (ON) transection, activating caspase-3. In the present study, we report that caspase-9, known to be an important activator of caspase-3, becomes activated in the axotomized adult rat retina as revealed by immunoblot analysis and protease activity assays. Reduction of caspase-9 activity by repeated intraocular injection of specific inhibitors significantly prevented RGC death. Caspase-9 activity was effectively blocked by inhibitor treatment and by application of IGF-I and BDNF, neurotrophic factors which have been shown to be highly neuroprotective in this model. Taken together, our data suggest that caspase-9 plays a critical role in apoptosis induction in axotomized RGCs in vivo and is regulated under treatment with growth and survival factors. Thus, providing more insight into the mechanisms underlying neuronal death and survival following trauma might serve as a basis to improve future therapeutic strategies preventing or at least reducing the severe consequences of neuronal injury. (C) 2000 Elsevier Science BN. All rights reserved.