ArticleThe Journal of biological chemistry2009
Intracellular trypsin induces pancreatic acinar cell death but not NF-kappaB activation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 82 citations in OpenAlex.
- From single-pathway cascade to network pathophysiology: how genetically engineered mouse models reshaped our understanding of pancreatitis.Frontiers in physiology · 2026Review
- Review
- Deletion of the WD40 domain of ATG16L1 exacerbates acute pancreatitis, abolishes LAP-like non-canonical autophagy and slows trypsin degradation.Autophagy · 2025Article
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.Journal of experimental & clinical cancer research : CR · 2023Article
- Sphingosine 1-phosphate receptor 2 mediated early stages of pancreatic and systemic inflammatory responses via NF-kappa B activation in acute pancreatitis.Cell communication and signaling : CCS · 2022Article
- New insights into the etiology, risk factors, and pathogenesis of pancreatitis in dogs: Potential impacts on clinical practice.Journal of veterinary internal medicine · 2022Review
- Article
- LCC-09, a Novel Salicylanilide Derivative, Exerts Anti-Inflammatory Effect in Vascular Endothelial Cells.Journal of inflammation research · 2021Article
- Trypsin activity governs increased susceptibility to pancreatitis in mice expressing human PRSS1R122H.The Journal of clinical investigation · 2020Article
- Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Genetics, Cell Biology, and Pathophysiology of Pancreatitis.Gastroenterology · 2019Review
- Intracellular rupture, exocytosis and actin interaction of endocytic vacuoles in pancreatic acinar cells: initiating events in acute pancreatitis.The Journal of physiology · 2018Article
- Hepatic alcohol dehydrogenase deficiency induces pancreatic injury in chronic ethanol feeding model of deer mice.Experimental and molecular pathology · 2018Article
- The Differential Role of Human Cationic Trypsinogen (Gastroenterology research and practice · 2017Review
- The Protective Effect of Alpha 7 Nicotinic Acetylcholine Receptor Activation on Critical Illness and Its Mechanism.International journal of biological sciences · 2017Review
- Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events.Biochimica et biophysica acta · 2016Article
- Exposure to Radiocontrast Agents Induces Pancreatic Inflammation by Activation of Nuclear Factor-κB, Calcium Signaling, and Calcineurin.Gastroenterology · 2015Article
- Redox signaling in acute pancreatitis.Redox biology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Premature intracellular activation of the digestive enzyme trypsinogen is considered to be the initiating event in pancreatitis. However, the direct consequences of intracellular trypsin activity have not previously been examined. In the current study, a mutant trypsinogen (paired basic amino acid cleaving enzyme (PACE)-trypsinogen), which is activated intracellularly by the endogenous protease PACE, was developed. This new construct allowed for the first time direct examination of the effects of intracellular trypsin on pancreatic acinar cells. We found that PACE-trypsinogen was expressed in the secretory pathway and was activated within acinar cells. Expression of PACE-trypsinogen induced apoptosis of HEK293 cells and pancreatic acinar cells, as indicated by histology, DNA laddering, PARP cleavage, and caspase-3 activation. Cell death was blocked by the trypsin inhibitor Pefabloc but not by the pancaspase inhibitor benzyloxycarbonyl-VAD, indicating that caspase-independent pathways were also involved. However, intracellular trypsin had no significant effect on the activity of the proinflammatory transcription factor NF-kappaB. In contrast, extracellular trypsin caused cell damage and dramatically increased NF-kappaB activity. These data indicate that localization of active trypsin determines its effects on pancreatic acinar cells. This new model will greatly improve our understanding of the role of active trypsin in pancreatitis and its associated inflammatory response.
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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.