Characterization of apoptosis-genes associated with NMDA mediated cell death in the adult rat retina

Characterization of apoptosis-genes associated with NMDA mediated cell death in the adult rat retina
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DOI:
10.1016/s0169-328x(01)00116-4
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发表时间:
2001-07-13
期刊:
MOLECULAR BRAIN RESEARCH
影响因子:
--
通讯作者:
Cooper, NGF
Cooper, NGF
中科院分区:
其他
文献类型:
--
作者:
Laabich, A;Li, GY;Cooper, NGF

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含有核定位信号(camkii - α (B))的钙/钙调素依赖性蛋白激酶II在暴露于n-甲基-d -天冬氨酸(NMDA)的视网膜神经元中发生改变。AIP(肉豆蔻酰基化自cam肽2相关抑制肽)是CaMKII的特异性抑制剂,可对nmda介导的神经毒性提供神经保护。在这项研究中,使用基因阵列来研究暴露于NMDA后哪些凋亡相关基因发生了改变。数据表明,5个编码蛋白的基因表达增加(2-7倍),这些蛋白可能参与NMDA诱导的细胞死亡。上调的基因有:FasL;GADD45;GADD153;Nur77和TNF-R1。AIP治疗阻断了它们改变的表达。结果表明,nmda诱导的兴奋性毒性涉及多个基因,而CaMKII的特异性抑制剂AIP调节视网膜中这些凋亡相关基因的表达。(C) 2001年Elsevier Science B.V.出版
Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal (CaMKII-alpha (B)) is altered in retinal neurons exposed to N-methyl-D-aspartate (NMDA). AIP (myristoylated autocamtide-2-related inhibitory peptide), a specific inhibitor of CaMKII provides neuroprotection against NMDA-mediated neurotoxicity. In this: study, gene-arrays were used to investigate which apoptosis-associated genes are altered after exposure to NMDA. The data indicate an increased expression (2-7-fold) of five such genes encoding proteins that could be involved in NMDA induced cell death. The up-regulated genes are: FasL; GADD45; GADD153; Nur77 and TNF-R1. Treatment with AIP blocked their altered expression. The results suggest that multiples genes are involved in NMDA-induced excitotoxicity and that AIP, a specific inhibitor for CaMKII, regulates the expression of these apoptosis-associated genes in the retina. (C) 2001 Published by Elsevier Science B.V.