ArticleAlcoholism, clinical and experimental research2012
Alcohol disrupts endoplasmic reticulum function and protein secretion in hepatocytes.
Article in Alcoholism, clinical and experimental research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- A large-scale DNA methylation study of alcohol use identified robust associations and cell-type specific insights.Molecular psychiatry · 2026Article
- Mitochondrial Calcium Signaling in Hepatocyte Health and Disease.Cold Spring Harbor perspectives in biology · 2026Review
- RIP3 and MLKL regulate ER stress in alcohol-associated liver disease and pharmacological ER stress models: Insights beyond necroptosis.JHEP reports : innovation in hepatology · 2026Article
- An Update on Animal Models of Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- RIP3 and MLKL regulate Hepatic ER stress in alcohol-associated liver disease and pharmacological ER stress models: insights beyond necroptosis.bioRxiv : the preprint server for biology · 2025Article
- Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells.iScience · 2023Article
- Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions.International journal of molecular sciences · 2023Article
- Inhibition of Abelson Tyrosine-Protein Kinase 2 Suppresses the Development of Alcohol-Associated Liver Disease by Decreasing PPARgamma Expression.Cellular and molecular gastroenterology and hepatology · 2023Article
- Gut microbiota in alcohol-related liver disease: pathophysiology and gut-brain cross talk.Frontiers in pharmacology · 2023Review
- Embryonic alcohol exposure disrupts the ubiquitin-proteasome system.JCI insight · 2022Article
- Magnesium isoglycyrrhizinate attenuates acute alcohol-induced hepatic steatosis in a zebrafish model by regulating lipid metabolism and ER stress.Nutrition & metabolism · 2022Article
- Role of ER Stress in Xenobiotic-Induced Liver Diseases and Hepatotoxicity.Oxidative medicine and cellular longevity · 2022Review
- Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3.Frontiers in pharmacology · 2022Article
- Ipomoeassin-F disrupts multiple aspects of secretory protein biogenesis.Scientific reports · 2021Article
- Role of alcohol in pathogenesis of hepatitis B virus infection.World journal of gastroenterology · 2020Review
- Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish.Disease models & mechanisms · 2018Article
- Alcohol Induces Cellular Senescence and Impairs Osteogenic Potential in Bone Marrow-Derived Mesenchymal Stem Cells.Alcohol and alcoholism (Oxford, Oxfordshire) · 2017Article
- Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver.World journal of hepatology · 2017Article
- Key Events Participating in the Pathogenesis of Alcoholic Liver Disease.Biomolecules · 2017Review
- Effect of BI-1 on insulin resistance through regulation of CYP2E1.Scientific reports · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMany alcoholic patients have serum protein deficiency that contributes to their systemic problems. The unfolded protein response (UPR) is induced in response to disequilibrium in the protein folding capability of the endoplasmic reticulum (ER) and is implicated in hepatocyte lipid accumulation and apoptosis, which are associated with alcoholic liver disease (ALD). We investigated whether alcohol affects ER structure, function, and UPR activation in hepatocytes in vitro and in vivo.
methodsHepG2 cells expressing human cytochrome P450 2E1 and mouse alcohol dehydrogenase (VL-17A) were treated for up to 48 hours with 50 and 100 mM ethanol. Zebrafish larvae at 4 days postfertilization were exposed to 350 mM ethanol for 32 hours. ER morphology was visualized by fluorescence in cells and transmission electron microscopy in zebrafish. UPR target gene activation was assessed using quantitative PCR, in situ hybridization, and Western blotting. Mobility of the major ER chaperone, BIP, was monitored in cells by fluorescence recovery after photobleaching (FRAP).
resultsVL-17A cells metabolized alcohol yet only had slight activation of some UPR target genes following ethanol treatment. However, ER fragmentation, crowding, and accumulation of unfolded proteins as detected by immunofluorescence and FRAP demonstrate that alcohol induced some ER dysfunction despite the lack of UPR activation. Zebrafish treated with alcohol, however, showed modest ER dilation, and several UPR targets were significantly induced.
conclusionsEthanol metabolism directly impairs ER structure and function in hepatocytes. Zebrafish are a novel in vivo system for studying ALD.
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