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Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells

机译:雌二醇和孕酮对肿瘤坏死因子α诱导的人肝癌HuH-7细胞凋亡的影响

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Oxidative stress, including the generation of reactive oxygen species (ROS), is known to be involved in apoptosis. Preventing apoptosis may thereby induce a malignant transformation of liver tumor cells. Estradiol (E2) is a potent endogenous antioxidant. We examined the proapoptotic role of progesterone as well as the antiapoptotic role of E2 in human hepatoma HuH-7 cells in a state of early apoptosis induced by tumor necrosis factor (TNF) alpha. The TNF alpha-induced ROS generation, lipid peroxidation, antioxidant enzyme consumption, a proapoptotic predominant expression of Bcl-2 family proteins, and a disruption of mitochondrial membrane potential were all inhibited by E2, and then they were further stimulated by progesterone in HuH-7 cells. The inhibitory effects of E2 were blocked by coincubation with progesterone. Treatment with the progesterone receptor antagonist RU486 led to the blockage of the, progesterone-mediated responses to E2 pretreatment in TNF alpha-induced apoptosis. These findings demonstrate that E2 inhibits the TNF alpha-induced early apoptosis in hepatoma cells, by suppressing the oxidative stress processes, whereas progesterone acts in a manner opposite from the effects of E2, and the inhibitory effects of E2 were blocked by progesterone, thus leading to the apoptosis of hepatoma cells. (c) 2006 Elsevier Inc. All rights reserved.
机译:众所周知,氧化应激(包括活性氧(ROS)的产生)与细胞凋亡有关。预防细胞凋亡可以由此诱导肝肿瘤细胞的恶性转化。雌二醇(E2)是有效的内源性抗氧化剂。在肿瘤坏死因子(TNF)α诱导的早期凋亡状态下,我们检查了孕酮的促凋亡作用以及E2在人肝癌HuH-7细胞中的抗凋亡作用。 TNFα诱导的ROS生成,脂质过氧化,抗氧化酶的消耗,Bcl-2家族蛋白的促凋亡为主表达以及线粒体膜电位的破坏均被E2抑制,然后在HuH- 7格。通过与孕酮共温育来阻断E2的抑制作用。用孕酮受体拮抗剂RU486治疗导致TNFα诱导的细胞凋亡中孕酮介导的对E2预处理的反应被阻断。这些发现表明,E2通过抑制氧化应激过程而抑制了TNFα诱导的肝癌细胞的早期凋亡,而孕酮的作用与E2的作用相反,并且E2的抑制作用被孕酮阻断,从而导致对肝癌细胞的凋亡(c)2006 Elsevier Inc.保留所有权利。

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