title: Early proteins E6 and E7 of human papillomavirus may attenuate ischemia-reperfusion injury.
abstract: 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.
authors.affiliation: Department of Gynecologic Oncology, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Sima
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lü
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000627:therapeutic use*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000627:therapeutic use*; D050725:Papillomavirus E7 Proteins / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012097:Repressor Proteins / Q000627:therapeutic use*; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53