在KA诱导的兴奋毒性中,Procaspase-3的激活和脱化
Yong Liu1,2, Hui Yan2, Jia Zhang2
1School of Biological Sciences, Xuzhou Medical University, Xuzhou 221004, P.R. China.
Protein and peptide letters
|November 3, 2023
概括
凯尼酸 (KA) 通过激活 procaspase-3 导致神经元死亡,这是一种涉及脱的过程. 抑制这种脱化可以保护大鼠海马体免受KA诱导的兴奋毒性.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞死亡研究 细胞死亡研究
背景情况:
- 谷氨酸酸盐受体激活 (GluK2) 和随后的Fas联结体 (FasL) 上调导致caspase-3激活和缺血后的神经元死亡延迟.
- 以氧化为媒介的S-化可能会抑制前酶的激活,而脱化则会促进它.
研究的目的:
- 为了研究 prokaspase-3 脱和激活在酸 (KA) 诱导的 excitoxicity 在大鼠海马中的分子机制.
主要方法:
- 使用生物素切换方法检测到 procaspase-3 S-nitrosylation.
- 通过免疫阻塞和FasL表达的裂变评估了通过免疫阻塞和FasL表达的 procaspase-3激活.
- 使用Cresyl紫色和TUNEL染色在海马CA1和CA3子场中的量化亡类神经元死亡.
主要成果:
- KA诱导了剂量和时间依赖的 procaspase-3 激活,由 NS102.2 抑制.
- 在KA后3小时发生了普罗卡斯帕酶-3脱化,通过SNP和GSNO可逆.
- FasL ASODNs和氨酸减少酶 (TrxR) 抑制剂奥拉诺芬阻止了脱和激活,逆转了KA诱导的细胞死亡.
结论:
- 通过FasL和TrxR通路,KA触发了 procaspase-3 的脱和激活.
- 用auranofin,SNP或GSNO抑制 procaspase-3 脱化提供了对KA诱导激发毒性的神经保护.
- 普罗卡斯帕斯-3需要初始脱化才能激活,从而揭示了治疗兴奋毒性的机制.
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