Singh Mayank, Sharma Himani, Singh Neeta
Department of Biochemistry, All India Institute of Medical Science, New Delhi 110029, India.
Mitochondrion. 2007 Dec;7(6):367-73. doi: 10.1016/j.mito.2007.07.003. Epub 2007 Aug 9.
Cervical cancer is the most common cancer amongst females in India and is associated with high risk HPVs, reactive oxygen species (ROS), and excessive inflammation in most cases. ROS in turn affects the expression of pro- and anti-apoptotic proteins. The objective of the present study was to elucidate the effect of hydrogen peroxide (H(2)O(2)) on apoptotic signaling molecules in vitro. HeLa cell line expresses the Human papilloma virus - 18, E6 oncoprotein which causes the ubiquitin mediated degradation of p53 protein and is thus p53 deficient. p53 is known to act as a cellular stress sensor and triggers apoptosis. p73, a member of the p53 family also induces apoptosis in response to DNA damaging agents but unlike p53, it is infrequently mutated in human tumors. We demonstrate here, that in HeLa cells, apoptosis is triggered by H(2)O(2) via the mitochondrial pathway involving upregulation of p73, and its downstream target Bax. This was accompanied by upregulation of ERK, JNK, c-Myc, Hsp-70 and down regulation of anti-apoptotic Bcl-XL, release of cytochrome c from mitochondria and activation of caspases-9 and -3.
宫颈癌是印度女性中最常见的癌症，在大多数情况下与高危型人乳头瘤病毒（HPV）、活性氧（ROS）和过度炎症相关。ROS反过来会影响促凋亡蛋白和抗凋亡蛋白的表达。本研究的目的是阐明过氧化氢（H₂O₂）在体外对凋亡信号分子的影响。HeLa细胞系表达人乳头瘤病毒18型E6癌蛋白，该蛋白会导致p53蛋白的泛素介导降解，因此p53缺乏。已知p53作为细胞应激传感器并触发凋亡。p73是p53家族的成员，也会响应DNA损伤剂诱导凋亡，但与p53不同，它在人类肿瘤中很少发生突变。我们在此证明，在HeLa细胞中，H₂O₂通过涉及p73及其下游靶点Bax上调的线粒体途径触发凋亡。这伴随着ERK、JNK、c-Myc、Hsp-70的上调以及抗凋亡蛋白Bcl-XL的下调、细胞色素c从线粒体的释放以及caspases-9和-3的激活。
