过氧化氢通过线粒体途径诱导HeLa细胞凋亡

Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway

 

抽象

宫颈癌是印度女性中最常见的癌症，并且在大多数情况下与高风险HPV，活性氧（ROS）和过度炎症相关。

ROS反过来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）对体外凋亡信号分子的影响。 HeLa细胞系表达人乳头瘤病毒-18，E6癌蛋白，其导致泛素介导的p53蛋白降解，因此p53缺陷。已知p53充当细胞应激传感器并触发细胞凋亡。 p73是p53家族的成员，也可以诱导细胞凋亡以应对DNA损伤剂，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，细胞凋亡是由H2O2通过线粒体途径触发的，涉及p73及其下游靶Bax的上调。这伴随着ERK，JNK，c-Myc，Hsp-70的上调和抗凋亡Bcl-XL的下调，细胞色素c从线粒体的释放和胱天蛋白酶-9和-3的活化。

　

Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway

　

Abstract

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 (H2O2) 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 H2O2 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.

　

SOURCE:

Author links open overlay panelMayankSinghHimaniSharmaNeetaSingh

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https://doi.org/10.1016/j.mito.2007.07.003Get rights and content

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Keywords

HeLaH2O2p73BaxApoptosis

Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway - ScienceDirect  https://www.sciencedirect.com/science/article/pii/S1567724907001183