摘要
蛋白磷酸酶2A(protein phosphatase 2A,PP2A)是蛋白磷酸酶家族的主要成员,在蛋白质可逆磷酸化过程中与蛋白激酶一样起着举足轻重的作用。自然界存在很多天然毒素可特异性地作用于PP2A从而影响体内蛋白质的可逆磷酸化,其中微囊藻毒素由于急性肝毒性和强促癌活性日益引起关注。尽管确切的机制仍未探明,但从目前的研究来看,微囊藻毒素产生毒性的机制可能与其引起细胞氧化应激、DNA损伤、细胞骨架的破坏以及诱导细胞凋亡相关。而PP2A在氧化应激、DNA损伤修复及维持细胞骨架稳态中起着重要作用,并能调控凋亡相关激酶CaMKII和Bcl-2家族蛋白,这对更好地理解微囊藻毒素LR如何通过影响PP2A而产生毒作用提供了新思路。
Protein phosphatase 2A （PP2A） is a main serine/threonine protein phosphatase responsible for a major portion of the total phosphatase activity, playing an equally important role in the regulation of protein phospho- rylation as protein kinases. Microcystin-LR （MC-LR）, one of the great deal of natural occurring toxins targeting PP2A, has been highly concerned due to its acute hepatotoxicity and potent tumor promotion activity. Although extensive studies indicate that oxidative stress, DNA damage, cytoskeleton disruption and apoptosis play pivotal role in the toxic effects of MC-LR, the exact mechanisms of MC-LR toxicity need to be fully elucidated. Due to the important functions of PP2A in the processes of oxidative stress, repair of DNA damage, cytoskeleton organization and the regulation of apoptosis related kinase CaMKII and Bcl-2 family members, we propose that MC-LR induces toxic effects by interacting with PP2A, which will shed lights on the molecular toxicity mechanisms of MC-LR.
出处
《中国细胞生物学学报》
CAS
CSCD
2010年第1期24-30,共7页
Chinese Journal of Cell Biology
基金
国家自然科学基金资助项目(No.30771827
No.20777067)~~
关键词
蛋白磷酸酶2A
微囊藻毒素
毒性效应
致毒机制
protein phosphatase 2A
microcystin
oxidative stress
toxic effects
machanism of toxicity
