Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde
Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde
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DOI：
10.1093/carcin/19.7.1275
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发表时间：
1998-07-01
期刊：
影响因子：
4.7
通讯作者：
Pietenpol, JA
中科院分区：
文献类型：
--
作者：
Ji, C;Rouzer, CA;Pietenpol, JA
我们研究了内源性遗传毒素丙二醛（MDA）对细胞周期动力学和几个细胞周期调控蛋白的表达和生化活性的影响。MDA处理两种人类细胞系（RKO和H1299）导致主要可检测的MDA-DNA加合物M（1）G-dR的水平升高3- 6倍，M1 G-dR的增加伴随着不可逆的细胞周期停滞，p53和p21蛋白水平升高，以及细胞周期蛋白E和细胞周期蛋白B相关激酶活性的抑制。细胞周期蛋白E和细胞周期蛋白B依赖性激酶活性的降低分别是由p21水平升高和cdc 2水平降低引起的。在RKO（野生型p53）和H1299（p53-null）细胞中观察到相当水平的p21诱导。因此，当MDA在产生与人体组织中发现的相同量级的M（1）G-dR水平的浓度下使用时，MDA能够在人体细胞系中参与细胞周期检查点功能。
We have investigated the effect of the endogenous genotoxin malondialdehyde (MDA) on cell cycle kinetics and the expression and biochemical activity of several cell cycle regulatory proteins. MDA treatment of two human cell lines (RKO and H1299) resulted in a 3- to 6-fold elevation in the levels of the major detectable MDA-DNA adduct, M(1)G-dR. The increase in M1G-dR was accompanied by irreversible cell cycle arrest, elevation in p53 and p21 protein levels, and inhibition of cyclin E- and cyclin B-associated kinase activities. The decrease in cyclin E- and cyclin B-dependent kinase activities was caused by increased p21 and decreased cdc2 levels, respectively. Comparable levels of p21 induction were observed in RKO (wild-type p53) and H1299 (p53-null) cells. Thus, MDA was able to engage cell cycle checkpoint function in human cell lines when used at concentrations that produce M(1)G-dR levels of the same magnitude found in human tissues.