Cargando…
Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas
Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to et...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342343/ https://www.ncbi.nlm.nih.gov/pubmed/27527870 http://dx.doi.org/10.18632/oncotarget.11103 |
_version_ | 1782513157490606080 |
---|---|
author | Ren, Zhenhua Wang, Xin Xu, Mei Yang, Fanmuyi Frank, Jacqueline A. Ke, Zun-ji Luo, Jia |
author_facet | Ren, Zhenhua Wang, Xin Xu, Mei Yang, Fanmuyi Frank, Jacqueline A. Ke, Zun-ji Luo, Jia |
author_sort | Ren, Zhenhua |
collection | PubMed |
description | Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein B1 (HMGB1). Ethanol altered the function of the pancreas which was indicated by altered levels of alpha-amylase, glucose and insulin. Ethanol exposure stimulated cell proliferation in the acini, suggesting an acinar regeneration. Ethanol caused pancreatic inflammation which was indicated by the induction of TNF-alpha, IL-1beta, IL-6, MCP-1 and CCR2, and the increase of CD68 positive macrophages in the pancreas. Ethanol-induced endoplasmic reticulum stress was demonstrated by a significant increase in ATF6, CHOP, and the phosphorylation of PERK and eiF-2alpha. In addition, ethanol increased protein oxidation, lipid peroxidation and the expression of iNOS, indicating oxidative stress. Therefore, this paradigm of binge ethanol exposure caused a spectrum of tissue injury and cellular stress to the pancreas, offering a good model to study alcoholic pancreatitis. |
format | Online Article Text |
id | pubmed-5342343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53423432017-03-22 Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas Ren, Zhenhua Wang, Xin Xu, Mei Yang, Fanmuyi Frank, Jacqueline A. Ke, Zun-ji Luo, Jia Oncotarget Research Paper: Pathology Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein B1 (HMGB1). Ethanol altered the function of the pancreas which was indicated by altered levels of alpha-amylase, glucose and insulin. Ethanol exposure stimulated cell proliferation in the acini, suggesting an acinar regeneration. Ethanol caused pancreatic inflammation which was indicated by the induction of TNF-alpha, IL-1beta, IL-6, MCP-1 and CCR2, and the increase of CD68 positive macrophages in the pancreas. Ethanol-induced endoplasmic reticulum stress was demonstrated by a significant increase in ATF6, CHOP, and the phosphorylation of PERK and eiF-2alpha. In addition, ethanol increased protein oxidation, lipid peroxidation and the expression of iNOS, indicating oxidative stress. Therefore, this paradigm of binge ethanol exposure caused a spectrum of tissue injury and cellular stress to the pancreas, offering a good model to study alcoholic pancreatitis. Impact Journals LLC 2016-08-05 /pmc/articles/PMC5342343/ /pubmed/27527870 http://dx.doi.org/10.18632/oncotarget.11103 Text en Copyright: © 2016 Ren et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Pathology Ren, Zhenhua Wang, Xin Xu, Mei Yang, Fanmuyi Frank, Jacqueline A. Ke, Zun-ji Luo, Jia Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title | Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title_full | Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title_fullStr | Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title_full_unstemmed | Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title_short | Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
title_sort | binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas |
topic | Research Paper: Pathology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342343/ https://www.ncbi.nlm.nih.gov/pubmed/27527870 http://dx.doi.org/10.18632/oncotarget.11103 |
work_keys_str_mv | AT renzhenhua bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT wangxin bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT xumei bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT yangfanmuyi bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT frankjacquelinea bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT kezunji bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas AT luojia bingeethanolexposurecausesendoplasmicreticulumstressoxidativestressandtissueinjuryinthepancreas |