在 postsynaptic 密度的后缺血性 ubiquitination 可逆地影响缺血相关激酶的活性
Luvna Dhawka1, Victoria Palfini1, Emma Hambright1
1Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Communications biology
|March 14, 2024
概括
缺血性中风增加了蛋白质的无处不在,特别是影响了像激酶这样的突触后密度蛋白. 乌比基因化调节激酶活性,影响中风后的神经元的存活.
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
- 生物化学 生物化学
背景情况:
- 乌比基的修改调节了蛋白质的功能和稳定性,这对细胞平衡至关重要,特别是在压力期间.
- 缺血性中风会在缺血外围的可活细胞中触发蛋白质泛化,但涉及的特定蛋白质仍未确定.
研究的目的:
- 通过蛋白质组学方法在经历缺血性中风的小鼠中识别无处不在的蛋白质.
- 为了研究在缺血性中风后的 postsynaptic密度 (PSD) 中调节激酶活性中的ubiquitination的作用.
主要方法:
- 在缺血性中风的小鼠模型中,蛋白质组学分析以确定无处不在的蛋白质.
- -蛋白质组学,以评估蛋白质酸化模式的变化.
- 在移除泛素之前和之后,对特定激酶 (CaMKII,PKC,Cdk5,Pyk2) 的活性测定.
主要成果:
- 确定了198种蛋白质,在中风后随处可见度增加,许多蛋白质局部化在PSD.
- 关键的PSD蛋白质,包括PSD95,NMDA/AMPA受体子单元和激酶 (CaMKII,PKC,Cdk5,Pyk2),显示出高的无处不在.
- 脑卒中改变了激酶活动:CaMKII,PKC,Cdk5下降,而Pyk2增加.
- 移除乌比基因素恢复了激酶活动到中风前的水平,证实了作为调节机制的乌比基因化.
结论:
- 在缺血性中风后,乌比基因在调节PSD相关的激酶活性方面发挥着重要作用.
- 这种由ubiquitination调节的激酶是后缺血性神经元损伤的关键因素.
- 这些发现揭示了影响缺血性中风病理的激酶调节的新机制.
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