ArticleThe Journal of biological chemistry2016
Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- MiRNA-loaded MSC exosomes restore autophagy flux for acute pancreatitis therapy.Frontiers in immunology · 2025Pooled it
- Interleukin-1α Mediates Pancreatic Fibroblast Activation, Regulates Immune Cell Recruitment and Fibrosis in Acute and Chronic Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of the ER-cargo protein CLN8 increases severity of acute pancreatitis and upregulates ER-stress and ER-phagy.Molecular biomedicine · 2026Article
- Article
- Nanotherapy for Pancreatitis: From Single-Cell Targeting Toward Multicellular-Coordinated Regulation.International journal of nanomedicine · 2026Review
- The role of inflammation in the immune evasion of KRas.Frontiers in immunology · 2026Review
- Role of Interleukin-6 Mediated T Cell Activation in Experimental Acute Pancreatitis.Inflammation · 2025Article
- Biochemical analyses of cystatin-C dimers and cathepsin-B reveals a trypsin-driven feedback mechanism in acute pancreatitis.Nature communications · 2025Article
- Deletion of the E3 ubiquitin ligase LRSAM1 fosters intracellularFrontiers in cellular and infection microbiology · 2025Article
- An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death.Cell death & disease · 2024Article
- Trypsin in pancreatitis: The culprit, a mediator, or epiphenomenon?World journal of gastroenterology · 2024Review
- Molecular mechanism and potential role of mitophagy in acute pancreatitis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Initiation of acute pancreatitis in mice is independent of fusion between lysosomes and zymogen granules.Cellular and molecular life sciences : CMLS · 2024Article
- Elimination of intracellular CaInternational journal of molecular medicine · 2024Article
- Interleukin‑22 alleviates arginine‑induced pancreatic acinar cell injury via the regulation of intracellular vesicle transport system: Evidence from proteomic analysis.Experimental and therapeutic medicine · 2023Article
- Profile of Pancreatic and Ileal Microbiota in Experimental Acute Pancreatitis.Microorganisms · 2023Article
- Identification of Genes Related to Resistance to Ichthyophthirius multifiliis Based on Co-expression Network Analysis in Grass Carp.Marine biotechnology (New York, N.Y.) · 2023Article
- IRAK3-mediated suppression of pro-inflammatory MyD88/IRAK signaling affects disease severity in acute pancreatitis.Scientific reports · 2023Article
- Article
- The Role of Microbiota in Pancreatic Cancer.Cancers · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific.
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