Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following H2O2 exposure
Role of p53 in antioxidant defense of HPV-positive cervical carcinoma cells following H2O2 exposure
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DOI：
10.1242/jcs.002345
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Cho, Nam Hoon
中科院分区：
文献类型：
--
作者：
Ding, Boxiao;Chi, Sung Gil;Cho, Nam Hoon
在HPV阳性的宫颈癌细胞中，p53蛋白在功能上被E6癌蛋白拮抗。我们研究了p53在HPV阳性宫颈癌细胞系抗氧化防御中的可能作用。我们发现，SiHa细胞含有整合的HPV 16有更高的表达p53和表现出最大的抵抗H2 O2诱导的氧化损伤，与HeLa，CaSki和ME 180细胞系相比。p53的下调导致SiHa细胞中p53调节的抗氧化酶的抑制和细胞内ROS的升高。相反，在HeLa、CaSki和ME 180细胞系中，在抑制p53蛋白后，ROS水平不受影响。在轻度或重度H2 O2诱导的应激下，p53缺陷的SiHa细胞表现出比对照SiHa细胞高得多的ROS水平。此外，我们分析了H2 O2处理后的细胞活力和凋亡，发现p53缺陷使SiHa细胞对H2 O2损伤敏感。抑制p53导致DNA的过度氧化;与暴露于相同水平的H2 O2攻击的p53缺陷SiHa细胞相比，对照SiHa细胞表现出更快地从DNA中去除8-氧代-7，8-二氢-2 '-脱氧鸟苷。这些数据共同表明，SiHa细胞中的内源性p53具有抗氧化功能，并参与抗氧化防御的增强。
In HPV-positive cervical carcinoma cells, p53 protein is functionally antagonized by the E6 oncoprotein. We investigated a possible role of p53 in antioxidant defense of HPV-positive cervical cancer cell lines. We found that SiHa cells containing integrated HPV 16 had higher expression of p53 and exhibited the greatest resistant to H2O2-induced oxidative damage, compared with HeLa, CaSki and ME180 cell lines. Downregulation of p53 resulted in the inhibition of p53-regulated antioxidant enzymes and elevated intracellular ROS in SiHa cells. By contrast, the ROS level was not affected in HeLa, CaSki and ME180 cell lines after inhibition of the p53 protein. Under mild or severe H2O2-induced stress, p53-deficient SiHa cells exhibited much higher ROS levels than control SiHa cells. Furthermore, we analyzed cell viability and apoptosis after H2O2 treatment and found that p53 deficiency sensitized SiHa cells to H2O2 damage. Inhibition of p53 resulted in excessive oxidation of DNA; control SiHa cells exhibited a more rapid removal of 8-oxo-7,8-dihydro-2 '-deoxyguanosine from DNA compared with p53-deficient SiHa cells exposed to the same level of H2O2 challenge. These data collectively show that endogenous p53 in SiHa cells has an antioxidant function and involves in the reinforcement of the antioxidant defense.