ArticleProceedings of the National Academy of Sciences of the United States of America2009
Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
- Mitochondrial dysfunction as a bridge to pathology in acute pancreatitis: From molecular insights to novel therapeutic strategies.World journal of gastroenterology · 2025Review
- The role of CaCell calcium · 2023Review
- Watching Living Cells in Action in the Exocrine Pancreas: The Palade Prize Lecture.Function (Oxford, England) · 2023Review
- Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis.International journal of molecular sciences · 2022Article
- Astrocytic IPFrontiers in cellular neuroscience · 2021Review
- Effect of Docosahexaenoic Acid on CaNutrients · 2019Article
- Genetics, Cell Biology, and Pathophysiology of Pancreatitis.Gastroenterology · 2019Review
- Research Progress on the Relationship Between Acute Pancreatitis and Calcium Overload in Acinar Cells.Digestive diseases and sciences · 2019Review
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- New insights into the pathways initiating and driving pancreatitis.Current opinion in gastroenterology · 2016Article
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- Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.Scientific reports · 2016Article
- Alcoholic pancreatitis: New insights into the pathogenesis and treatment.World journal of gastrointestinal pathophysiology · 2016Review
- Ca(2+) signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca(2+) channel blockade.The Journal of physiology · 2016Article
- Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Redox signaling in acute pancreatitis.Redox biology · 2015Review
- The ryanodine receptor is expressed in human pancreatic acinar cells and contributes to acinar cell injury.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Decoding calcium signaling across the nucleus.Physiology (Bethesda, Md.) · 2014Review
- Molecular mechanisms of alcohol associated pancreatitis.World journal of gastrointestinal pathophysiology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Toxic alcohol effects on pancreatic acinar cells, causing the often fatal human disease acute pancreatitis, are principally mediated by fatty acid ethyl esters (non-oxidative products of alcohol and fatty acids), emptying internal stores of Ca(2+). This excessive Ca(2+) liberation induces Ca(2+)-dependent necrosis due to intracellular trypsin activation. Our aim was to identify the specific source of the Ca(2+) release linked to the fatal intracellular protease activation. In 2-photon permeabilized mouse pancreatic acinar cells, we monitored changes in the Ca(2+) concentration in the thapsigargin-sensitive endoplasmic reticulum (ER) as well as in a bafilomycin-sensitive acid compartment, localized exclusively in the apical granular pole. We also assessed trypsin activity in the apical granular region. Palmitoleic acid ethyl ester (POAEE) elicited Ca(2+) release from both the ER as well as the acid pool, but trypsin activation depended predominantly on Ca(2+) release from the acid pool, that was mainly mediated by functional inositol 1,4,5- trisphosphate receptors (IP(3)Rs) of types 2 and 3. POAEE evoked very little Ca(2+) release and trypsin activation when IP(3)Rs of both types 2 and 3 were knocked out. Antibodies against IP(3)Rs of types 2 and 3, but not type 1, markedly inhibited POAEE-elicited Ca(2+) release and trypsin activation. We conclude that Ca(2+) release through IP(3)Rs of types 2 and 3 in the acid granular Ca(2+) store induces intracellular protease activation, and propose that this is a critical process in the initiation of alcohol-related acute pancreatitis.
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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.