[英语，研究 ]HBx Sensitizes Cells to Oxidative Stress-induced Apoptosis by

StephenW

http://7thspace.com/headlines/379785/hbx_sensitizes_cells_to_oxidative_stress_induced_apoptosis_by_accelerating_the_loss_of_mcl_1_protein_via_caspase_3_cascade.html
HBx Sensitizes Cells to Oxidative Stress-induced Apoptosis by Accelerating the Loss of Mcl-1 Protein via Caspase-3 Cascade
Oxidative stress has been implicated in the pathogenesis of a wide spectrum of human diseases, including Hepatitis B virus (HBV)-related liver disease. Hepatitis B virus X protein (HBx) is a key regulator of HBV that exerts pleiotropic activity on cellular functions.

Recent studies showed that HBx alters mitochondrial membrane potential, thereby sensitizing cells to pro-apoptotic signals. However, it remains largely unknown whether susceptibility of hepatocytes could be disturbed by HBx under oxidative stress conditions.

The purpose of this study is to determine the apoptotic susceptibility of HBx-expressing hepatocytes upon exposure to pro-oxidant stimuli in vitro and in vivo and explore its underlying mechanism.

Results: Although expression of HBx itself did not activate apoptotic signaling, it significantly enhanced oxidative stress-induced cell death both in vitro and in vivo. Interestingly, this phenomenon was associated with a pronounced reduction of protein levels of Mcl-1, but not other anti-apoptotic Bcl-2 members.

Importantly, enforced expression of Mcl-1 prevented HBx-triggered cell apoptosis; conversely, specific knockdown of Mcl-1 exacerbated HBx-induced apoptosis upon exposure to oxidative stress. Furthermore, inhibition of caspase-3 not only abrogated HBx-triggered apoptotic killing but also blocked HBx-induced Mcl-1 loss.

Additionally, expression of HBx and Mcl-1 was found to be inversely correlated in HBV-related hepatocellular carcinogenesis (HCC) tissues.

Conclusions: Our findings indicate that HBx exerts pro-apoptotic effect upon exposure to oxidative stress probably through accelerating the loss of Mcl-1 protein via caspase-3 cascade, which may shed a new light on the molecular mechanism of HBV-related hepatocarcinogenesis.

Author: Liang HuLei ChenGuangZhen YangLiang LiHanYong SunYanXin ChangQianQian TuMengChao WuHongYang Wang
Credits/Source: Molecular Cancer 2011, 10:43



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StephenW

HBx的敏感性的细胞对氧化应激诱导的加速通过Caspase - 3的级联的Mcl - 1蛋白的丢失凋亡
氧化应激有牵连的一个范围广泛的人类疾病，其中包括乙型肝炎病毒（HBV）相关肝病的发病机制。乙型肝炎病毒X蛋白（HBx蛋白）是一种关键的调节乙型肝炎病毒对细胞功能的发挥多效性的活动。

最近的研究表明，HBx的改变线粒体膜电位，从而敏感细胞促凋亡信号。但是，它仍然是未知的肝细胞的敏感性，是否可以通过HBx蛋白氧化应激条件下不安。

本研究的目的是确定HBx蛋白，表达在接触亲氧化剂刺激在体外和体内，并探讨其作用机制肝细胞凋亡的易感性。

结果：虽然HBx蛋白的表达本身没有激活凋亡信号，它大大增强氧化应激诱导的细胞死亡在体外和体内。有趣的是，这种现象是与一个对的Mcl - 1蛋白水平明显降低，而不是其他抗凋亡Bcl - 2的成员。

重要的是，强迫的Mcl - 1的表达阻止HBx蛋白引发的细胞凋亡;相反，内侧副韧带，加剧HBx蛋白引起的暴露于氧化应激细胞凋亡的具体击倒。此外，caspase - 3的抑制，不仅废除HBx蛋白触发凋亡阻断HBx的杀害，但也引起韧带- 1负。

此外，HBx蛋白和Mcl - 1的表达被认为是在HBV相关肝癌的发生（肝癌）组织呈负相关。

结论：我们的研究结果表明，HBx蛋白在接触氧化施加压力促凋亡作用，通过加快通过caspase - 3的叶栅损失的Mcl - 1蛋白，这可能揭示了乙肝病毒相关的肝癌发生的分子机制，以新的眼光可能。

作者：梁HuLei ChenGuangZhen阎良区LiHanYong SunYanXin ChangQianQian TuMengChao WuHongYang王
学分/来源：肿瘤分子2011，10:43

StephenW

刘老病毒 发表于 2011-4-20 16:48
你就装B吧，没用，怎么装也不是B。不爽拉来骂骂。

"没用" - 所有的作者是来自上海"东方肝胆外科医院", "交通大学", 你去告诉他们这研究是无用的.

Liang Hu,1, Lei Chen,1, Liang Li,1, HanYong Sun,1 GuangZhen Yang,1 YanXin Chang,1 QianQian Tu,1 MengChao Wu,2, and HongYang Wang1,3*International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute,1Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China,2State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai 200032, China3

bigben446

StephenW 发表于 2011-4-20 17:37
"没用" - 所有的作者是来自上海"东方肝胆外科医院", "交通大学", 你去告诉他们这研究是无用的.

Liang Hu ...

国内现在研究也一步一步上来了

lin12345