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

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 expre...

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Autores principales: Zhang, Chao, Ma, Teng, Luo, Tao, Li, Ang, Gao, Xiang, Wang, Zhong-Gao, Li, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840473/
https://www.ncbi.nlm.nih.gov/pubmed/29531462
http://dx.doi.org/10.3748/wjg.v24.i9.982
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author Zhang, Chao
Ma, Teng
Luo, Tao
Li, Ang
Gao, Xiang
Wang, Zhong-Gao
Li, Fei
author_facet Zhang, Chao
Ma, Teng
Luo, Tao
Li, Ang
Gao, Xiang
Wang, Zhong-Gao
Li, Fei
author_sort Zhang, Chao
collection PubMed
description 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. qPCR was used to examine the PARP1 expression in cell lines after treatment with H(2)O(2) and bile acids (pH 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 stress. RESULTS: 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, γH2AX, and poly(ADP-ribose) (PAR) was observed. H(2)O(2) and bile acids (pH 4) increased the PARP1 mRNA expression level in normal esophageal epithelial cells. Using shRNA-PARP1 to suppress PARP1 activity decreased the cell viability after treatment with H(2)O(2) and bile acids (pH 4), and increased the oxidative damage as demonstrated by an increase in the levels of H(2)O(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.
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spelling pubmed-58404732018-03-12 Dysregulation of PARP1 is involved in development of Barrett’s esophagus Zhang, Chao Ma, Teng Luo, Tao Li, Ang Gao, Xiang Wang, Zhong-Gao Li, Fei World J Gastroenterol Basic Study 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. qPCR was used to examine the PARP1 expression in cell lines after treatment with H(2)O(2) and bile acids (pH 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 stress. RESULTS: 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, γH2AX, and poly(ADP-ribose) (PAR) was observed. H(2)O(2) and bile acids (pH 4) increased the PARP1 mRNA expression level in normal esophageal epithelial cells. Using shRNA-PARP1 to suppress PARP1 activity decreased the cell viability after treatment with H(2)O(2) and bile acids (pH 4), and increased the oxidative damage as demonstrated by an increase in the levels of H(2)O(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. Baishideng Publishing Group Inc 2018-03-07 2018-03-07 /pmc/articles/PMC5840473/ /pubmed/29531462 http://dx.doi.org/10.3748/wjg.v24.i9.982 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Zhang, Chao
Ma, Teng
Luo, Tao
Li, Ang
Gao, Xiang
Wang, Zhong-Gao
Li, Fei
Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title_full Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title_fullStr Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title_full_unstemmed Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title_short Dysregulation of PARP1 is involved in development of Barrett’s esophagus
title_sort dysregulation of parp1 is involved in development of barrett’s esophagus
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840473/
https://www.ncbi.nlm.nih.gov/pubmed/29531462
http://dx.doi.org/10.3748/wjg.v24.i9.982
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