Dysregulation of PARP1 is involved in development of Barrett's esophagus

作     者：Chao Zhang Teng Ma Tao Luo Ang Li Xiang Gao Zhong-Gao Wang Fei Li 

作者机构：Department of General SurgeryXuanwu HospitalCapital Medical UniversityBeijing 100053China Beijing Institute of Radiation MedicineBeijing 100053China Department of Gastroesophageal Reflux DiseaseSecond Artillery General Hospital of Chinese People’s Liberation ArmyBeijing 100088China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2018年第24卷第9期

页      面：982-991页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by the National Natural Science Foundation of China,No.81470587 Beijing Municipal Natural Science Foundation of China,No.7162076 

主　　题：PARP1 Barrett’s esophagus DNA repair Oxidative damage Bile acids 

摘      要：AIM To investigate the potential role of poly(ADP-ribose) polymerase 1(PARP1) in the development of Barrett s esophagus(BE).METHODS A BE mouse model was established to examine the esophageal morphological changes and molecular changes. Microarray analysis was performed to compare the gene expression profiles between BE patients and healthy controls. q PCR was used to examine the PARP1 expression in cell lines after treatment with H_2O_2 and bile acids(p H 4). Immunofluorescence staining, comet assay, and annexin V staining were used to evaluate the impact of PARP1 activity on cell survival and DNA damage response after oxidative *** The gene expression profile in normal and BE esophageal epithelial cells showed that PARP1, the major poly(ADP-ribose) polymerase, was overexpressed in BE. In the mouse model of BE, positive staining for NF-κB, γH2 AX, and poly(ADP-ribose)(PAR) was observed. H_2O_2 and bile acids(p H 4) increased the PARP1 m RNA expression level in normal esophageal epithelial cells. Using sh RNA-PARP1 to suppress PARP1 activity decreased the cell viability after treatment with H_2O_2 and bile acids(p H 4), and increased the oxidative damage as demonstrated by an increase in the levels of H_2O_2 , intracellular reactive oxygen species(ROS), oxidative DNA damage, double-strand breaks, and apoptosis(P 0.01).CONCLUSION The dysfunction of PARP1 in esophageal epithelial cells increases the levels of ROS and oxidative DNA damage, which could be common risk factors for BE and esophageal adenocarcinoma.