Early proteins E6 and E7 of human papillomavirus may attenuate ischemia-reperfusion injury
Early proteins E6 and E7 of human papillomavirus may attenuate ischemia-reperfusion injury
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人乳头瘤病毒的早期蛋白E6和E7可能减轻缺血再灌注损伤
DOI：
10.1016/j.mehy.2011.01.013
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发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
Xie, Xing
中科院分区：
文献类型：
--
作者：
Sima, Ni;Lue, Weiguo;Xie, Xing
众所周知，人乳头瘤病毒（HPV）参与了宫颈癌等特定肿瘤的发病过程。实验和临床研究表明，早期蛋白E6和E7在宫颈癌的发生发展中起重要作用。HPV的早期蛋白E6和E7均是癌蛋白，它们使特定的抑癌蛋白p53和pRb失活，并干扰细胞凋亡以防止癌变。p53和pRb在调节细胞凋亡和阻止细胞永生化中起重要作用，但它们也介导缺血/再灌注相关的细胞凋亡并引起缺血-再灌注损伤（IRI）。一些研究表明，抑制细胞凋亡可能为改善缺血/再灌注中的IRI提供有希望的方法。小分子化学抑制剂和针对p53的siRNA都可以阻断p53依赖的凋亡，保护器官功能免受IRI的影响。同样，抑制pRb可以抑制缺血/再灌注相关的凋亡。基于这些研究，我们提出了一个新的假说，即HPV早期蛋白E6和E7通过抑制细胞凋亡和失活p53和pRb来减轻缺血再灌注损伤。这两种癌蛋白可能用于在特殊的临床条件下保护器官功能免受缺血-再灌注损伤，例如器官移植、中风、心肺转流和心肌梗死。(C)2011爱思唯尔有限公司保留所有权利。
It is well known that human papillomaviruses (HPVs) involve in the pathogenesis of some specific carcinomas such as cervical cancer. Experimental and clinical studies have shown that early proteins E6 and E7 played the most important role in the cervical carcinogenesis. Early proteins E6 and E7 of HPV both are oncoproteins for they disable specific tumor suppressor proteins, p53 and pRb, and disturb apoptosis against carcinogenesis. Both p53 and pRb play an important role in regulating apoptosis and preventing cell immortalization, but they also mediate ischemia/reperfusion-associated apoptosis and give rise to ischemia-reperfusion injury (IRI). Several studies showed inhibition of apoptosis may provide promising approaches to ameliorating IRI in ischemia/reperfusion. Both small-molecule chemical inhibitor and siRNA against p53 block p53-dependent apoptosis and protect organ function from IRI. Similarly, inhibiting pRb can restrain ischemia/reperfusion-associated apoptosis. Based on these studies, we propose a novel hypothesis that early proteins E6 and E7 of HPV attenuate ischemia-reperfusion injury by inhibiting apoptosis and inactivating p53 and pRb. It is possible that the two oncoproteins can be used to protect organ function from ischemia-reperfusion injury in special clinical conditions such as organ transplant, stroke, cardiopulmonary bypass, and myocardial infarction. (C) 2011 Elsevier Ltd. All rights reserved.