ArticleJournal of hepatology2018
Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Influence of Alcohol on the Intestinal Immune System.Alcohol research : current reviews · 2025Pooled it
- Ethanol, acetaldehyde, lipopolysaccharide, and neutrophil extracellular traps: four-pronged attack on gut epithelial barrier in alcohol use disorder.Anatomical record (Hoboken, N.J. : 2007) · 2026Review
- Opposing Roles of CYP2E1 and ALDH2 in Binge Alcohol-Mediated Cerebellar Damage.International journal of molecular sciences · 2026Article
- Therapeutic potential of panax ginseng-derived nanovesicles in osteoporosis through enhanced osteoblast.Journal of ginseng research · 2026Article
- Impact of PAR2 on Tight Junctions and Esophageal Mucosal Inflammation in Rats with Gastroesophageal Reflux Disease.Neurogastroenterology and motility · 2026Article
- Functional roles and regulatory mechanisms of paeonol in the treatment of liver disease.Natural products and bioprospecting · 2026Review
- Gut-Liver Axis Failure in Critical Alcohol-Associated Liver Disease: From ICU Secondary Hits to Microbiome-Targeted Therapy.Mediators of inflammation · 2026Review
- Article
- The Link between Alcohol Consumption and Kidney Injury.The American journal of pathology · 2026Review
- Early oxidative protein modifications and gut damage/leakiness contribute to drug-induced acute liver failure.Clinical and molecular hepatology · 2026Article
- Short-Term Alcohol Consumption Is Sufficient to Disrupt Microbial Communities and the Intestinal and Circulating Metabolites in a Non-Human Primate Model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Unraveling the Interplay Between Alcohol, Immunity, and Gastric Cancer: A Genomic Approach.Food science & nutrition · 2025Article
- Ginseng-derived exosome-like nanovesicles protect against liver fibrosis by regulating TIMP2 pathways and gut dysbiosis.Asian journal of pharmaceutical sciences · 2025Article
- Advances in the acting mechanism and treatment of gut microbiota in metabolic dysfunction-associated steatotic liver disease.Gut microbes · 2025Review
- Exploration of the optimal concentration of quercetin liposome nanoparticles for the treatment of liver damage.BMC pharmacology & toxicology · 2025Article
- Co-administration of polyethylene glycol with binge ethanol reduces markers of intestinal and hepatic inflammation in C57BL/6J mice by diminishing ethanol absorption through the intestinal wall.Alcohol, clinical & experimental research · 2025Article
- Exploration and Validation of Key Genes and Immune Infiltration in Alcoholic Hepatitis.Journal of inflammation research · 2025Article
- Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Review
- Therapeutic Effects ofNutrients · 2024Article
- Melatonin Prevents Thioacetamide-Induced Gut Leakiness and Liver Fibrosis Through the Gut-Liver Axis via Modulating Sirt1-Related Deacetylation of Gut Junctional Complex and Hepatic Proteins.Journal of pineal research · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsBinge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness.
methodsThe levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses.
resultsBinge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels.
conclusionsThese results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins, in promoting binge alcohol-induced gut leakiness and endotoxemia, contributing to inflammatory liver disease. LAY SUMMARY: Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury. Our results demonstrated for the first time the critical roles of apoptosis of enterocytes and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins in promoting this gut leakiness and endotoxemia. These results provide insight into the molecular mechanisms of alcohol-induced inflammatory liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.