ArticleGastroenterology2016
Release of Cathepsin B in Cytosol Causes Cell Death in Acute Pancreatitis.
Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 119 citations in OpenAlex.
- Unraveling the Link Between Azathioprine and Acute Pancreatitis: Integrating Network Toxicology, Machine Learning, and Mendelian Randomization.CPT: pharmacometrics & systems pharmacology · 2026Article
- Acute pancreatitis: mechanisms and therapeutic approaches.Signal transduction and targeted therapy · 2026Review
- Article
- Post-translational modification crosstalk in acute pancreatitis: linking acinar stress to innate immune amplification and tissue repair.Frontiers in immunology · 2026Review
- The role of inflammation in the immune evasion of KRas.Frontiers in immunology · 2026Review
- A recurrence prediction model based on serological indicators in children with acute pancreatitis without pancreaticobiliary anatomical abnormalities.Frontiers in pediatrics · 2026Article
- Acute pancreatitis: Translating early mechanisms to bedside management.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Review
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- Development and validation of dynamic clinical subphenotypes in acute pancreatitis patients using vital sign trajectories in intensive care units: a multinational cohort study.Signal transduction and targeted therapy · 2025Article
- The mycotoxin Beauvericin is an uncompetitive inhibitor of Cathepsin B.Protein science : a publication of the Protein Society · 2025Article
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- Biochemical analyses of cystatin-C dimers and cathepsin-B reveals a trypsin-driven feedback mechanism in acute pancreatitis.Nature communications · 2025Article
- Lysine acetylation and its role in the pathophysiology of acute pancreatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Overview of the cellular and immune mechanisms involved in acute pancreatitis: In search of new prognosis biomarkers.Expert reviews in molecular medicine · 2025Review
- Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis.Open medicine (Warsaw, Poland) · 2025Article
- Inhibition of cathepsin L ameliorates inflammation through the A20/NF-κB pathway in endotoxin-induced acute lung injury.iScience · 2024Article
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- The TRIM28/miR133a/CD47 axis acts as a potential therapeutic target in pancreatic necrosis by impairing efferocytosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Molecular mechanism and potential role of mitophagy in acute pancreatitis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Long-chain fatty acids - The turning point between 'mild' and 'severe' acute pancreatitis.Heliyon · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsExperimental studies in acute pancreatitis (AP) suggest a strong association of acinar cell injury with cathepsin B-dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death is not clear. In this study, we have explored intra-acinar events downstream of trypsin activation that lead to acinar cell death.
methodsAcinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen 7, or cathepsin B-deleted) were stimulated with supramaximal cerulein, and the cytosolic activity of cathepsin B and trypsin was evaluated. Permeabilized acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis.
resultsBoth in vitro and in vivo studies have suggested that during AP cathepsin B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin B into the cytosol can lead to cell death through necrosis.
conclusionsThis report defines the role of trypsin in AP and shows that cytosolic cathepsin B but not trypsin activates cell death pathways. This report also suggests that trypsin is a requisite for AP only because it causes release of cathepsin B into the cytosol.
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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.