4-hydroxynonenal affects pRb/E2F pathway in HL-60 human leukemic cells
4-hydroxynonenal affects pRb/E2F pathway in HL-60 human leukemic cells
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DOI：
10.1016/s0006-291x(02)00649-6
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发表时间：
2002-07-12
影响因子：
3.1
通讯作者：
Dianzani, MU
中科院分区：
文献类型：
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作者：
Barrera, G;Pizzimenti, S;Dianzani, MU
4-羟基壬烯醛(HNE)是一种高活性的脂质过氧化产物，在多种肿瘤细胞系中具有抗增殖作用，并可引起HL-60细胞周期进程的改变。HNE下调K562、HL-60和MEL细胞c-myc的表达。这促使我们研究了从CKIs的表达和pRb的磷酸化开始，到达c-myc基因P2启动子中的共同序列的E2F结合的级联现象。HNE(1um)处理HL-60细胞后，p21(WAF1/CIP1)表达增加，pRb去磷酸化，小分子E2F复合体减少，与P2c-myc启动子结合的大分子E2F复合体增多。HNE处理降低了E2F4的表达，减少了pRb/E2F4复合体的数量，而增加了pRb/E2F1复合体的数量。综上所述，HNE可以通过改变与细胞增殖调控有关的几个基因的表达来影响pRb/E2F通路。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
4-Hydroxynonenal (HNE), a highly reactive product of lipid peroxidation, has an antiproliferative effect in several tumor cell lines and provokes alteration of cell cycle progression in HL-60 cells. HNE down-regulates c-myc expression in K562, HL-60, and MEL cells. This prompted us to study the cascade of phenomena that, starting from the CKIs expression and the phosphorylation of pRb, arrives at the E2F binding to consensus sequence in the P2 promoter of the c-myc gene. Treatment of HL-60 cells with HNE (1 muM) causes a p53-independent increase of p21(WAF1/CIP1) expression, pRb dephosphorylation, a decrease of low molecular weight E2F complexes and an increase of high molecular weight E2F complexes bound to P2 c-myc promoter. E2F4 expression is reduced by HNE treatment as well as the amount of pRb/E2F4 complexes, whereas the amount of pRb/E2F1 complexes is increased. In conclusion, HNE can affect the pRb/E2F pathway by modifying the expression of several genes involved in the control of cell proliferation. (C) 2002 Elsevier Science (USA). All rights reserved.