Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas

Zhenhua Ren; Xin Wang; Mei Xu; Fanmuyi Yang; Jacqueline A Frank; Zun-Ji Ke; Jia Luo

doi:10.18632/oncotarget.11103

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Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas

Journal article

Open access

Peer reviewed

Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas

Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A Frank, Zun-Ji Ke and Jia Luo

Oncotarget, Vol.7(34), pp.54303-54316

08/23/2016

DOI: 10.18632/oncotarget.11103

PMCID: PMC5342343

PMID: 27527870

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Abstract

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.

Alcoholism - complications

Alcoholism - metabolism

Animals

Endoplasmic Reticulum Stress - physiology

HMGB1 Protein - analysis

Keratin-18 - analysis

Male

Mice

Mice, Inbred C57BL

Oxidative Stress

Pancreas - pathology

Pancreatitis, Alcoholic - etiology

Details

Title: Subtitle: Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas
Creators: Zhenhua Ren - University of Kentucky
Xin Wang - University of Kentucky
Mei Xu - University of Kentucky
Fanmuyi Yang - University of Kentucky
Jacqueline A Frank - University of Kentucky
Zun-Ji Ke - Shanghai University of Traditional Chinese Medicine
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: Oncotarget, Vol.7(34), pp.54303-54316
DOI: 10.18632/oncotarget.11103
PMID: 27527870
PMCID: PMC5342343
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Grant note: I01 BX001721 / BLRD VA P30 CA177558 / NCI NIH HHS R01 AA015407 / NIAAA NIH HHS R01 AA017226 / NIAAA NIH HHS
Language: English
Date published: 08/23/2016
Academic Unit: Pathology
Record Identifier: 9984201254502771

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