ArticleProceedings of the National Academy of Sciences of the United States of America2004
Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid metabolites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 214 citations in OpenAlex.
- Conceptual framework and expert guidance on intrapancreatic fat deposition: the Melbourne consensus.Nature reviews. Gastroenterology & hepatology · 2026Review
- Effects of Ethanol and Opioid Receptor Antagonists Naltrexone and LY2444296 on the Organization of Cholesterol- and Sphingomyelin-Enriched Plasma Membrane Domains.ACS chemical neuroscience · 2025Article
- Phosphate Improves Mitochondrial Function and Reduces Pancreatitis in Hypertriglyceridemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Acute pancreatitis experimental models, advantages and disadvantages.Journal of physiology and biochemistry · 2025Review
- Repurposing BCL2 inhibitors: Venetoclax protects against acinar cell necrosis in acute pancreatitis by promoting apoptosis.Cell death & disease · 2025Article
- Article
- Alcohol intake and pancreatic cancer risk: An analysis from 30 prospective studies across Asia, Australia, Europe, and North America.PLoS medicine · 2025Article
- The exposome as a target for primary prevention and a tool for early detection of pancreatic cancer.Best practice & research. Clinical gastroenterology · 2025Review
- MCU-Mediated SIRT3 Inhibition Drives Oxidative Stress-Induced Cytoskeletal Disruption in Pancreatic Ductal Epithelium: A Mechanism of Hypertriglyceridemic Acute Pancreatitis.International journal of general medicine · 2025Article
- Deletion of the WD40 domain of ATG16L1 exacerbates acute pancreatitis, abolishes LAP-like non-canonical autophagy and slows trypsin degradation.Autophagy · 2025Article
- Naltrexone blocks alcohol-induced effects on kappa-opioid receptors in the plasma membrane.Translational psychiatry · 2024Article
- Triglyceride-lowering therapies in hypertriglyceridemia-associated acute pancreatitis in China: a multicentre prospective cohort study.BMC medicine · 2024Article
- Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis.Clinical and translational medicine · 2024Article
- Lifestyle Medicine for the Prevention and Treatment of Pancreatitis and Pancreatic Cancer.Diagnostics (Basel, Switzerland) · 2024Review
- Modifiable Pancreatic Ductal Adenocarcinoma (PDAC) Risk Factors.Journal of clinical medicine · 2023Review
- Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.Journal of translational medicine · 2023Review
- The 2022 George E Palade Medal Lecture: Toxic CaPancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Review
- Comprehensive review on the pathogenesis of hypertriglyceridaemia-associated acute pancreatitis.Annals of medicine · 2023Review
- Watching Living Cells in Action in the Exocrine Pancreas: The Palade Prize Lecture.Function (Oxford, England) · 2023Review
- Malondialdehyde-Acetaldehyde Extracellular Matrix Protein Adducts Attenuate Unfolded Protein Response During Alcohol and Smoking-Induced Pancreatitis.Gastroenterology · 2022Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ethanol causes pancreatic damage by an unknown mechanism. Previously, we demonstrated that a sustained rise of the cytosolic Ca(2+) concentration ([Ca(2+)](i)) causes pancreatic acinar cell injury. Here we have investigated the effects of ethanol and its metabolites on Ca(2+) signaling in pancreatic acinar cells. Most cells exposed to ethanol (up to 850 mM) showed little or no increase in [Ca(2+)](i) (and never at concentrations <50 mM). During sustained exposure to 850 mM ethanol, acetylcholine (ACh) evoked a normal [Ca(2+)](i) elevation and following ACh removal there was a normal and rapid recovery to a low resting level. The oxidative metabolite acetaldehyde (up to 5 mM) had no effect, whereas the nonoxidative unsaturated metabolite palmitoleic acid ethyl ester (10-100 microM, added on top of 850 mM ethanol) induced sustained, concentration-dependent increases in [Ca(2+)](i) that were acutely dependent on external Ca(2+) and caused cell death. These actions were shared by the unsaturated metabolite arachidonic acid ethyl ester, the saturated equivalents palmitic and arachidic acid ethyl esters, and the fatty acid palmitoleic acid. In the absence of external Ca(2+), releasing all Ca(2+) from the endoplasmic reticulum by ACh (10 microM) or the specific Ca(2+) pump inhibitor thapsigargin (2 microM) prevented such Ca(2+) signal generation. We conclude that nonoxidative fatty acid metabolites, rather than ethanol itself, are responsible for the marked elevations of [Ca(2+)](i) that mediate toxicity in the pancreatic acinar cell and that these compounds act primarily by releasing Ca(2+) from the endoplasmic reticulum.
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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.