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Release of Cathepsin B in Cytosol Causes Cell Death in Acute Pancreatitis.
Talukdar, Rupjyoti; Sareen, Archana; Zhu, Hongyan; Yuan, Zuobiao; Dixit, Ajay; Cheema, Hassam; George, John; Barlass, Usman; Sah, Raghuwansh; Garg, Sushil K; Banerjee, Sulagna; Garg, Pramod; Dudeja, Vikas; Dawra, Rajinder; Saluja, Ashok K.
Afiliación
  • Talukdar R; Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.
  • Sareen A; Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
  • Zhu H; Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
  • Yuan Z; Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
  • Dixit A; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • Cheema H; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • George J; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • Barlass U; Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
  • Sah R; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
  • Garg SK; Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
  • Banerjee S; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • Garg P; Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
  • Dudeja V; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • Dawra R; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
  • Saluja AK; Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida. Electronic address: asaluja@miami.edu.
Gastroenterology ; 151(4): 747-758.e5, 2016 10.
Article en En | MEDLINE | ID: mdl-27519471
BACKGROUND & AIMS: Experimental 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. METHODS: Acinar 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. RESULTS: Both 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. CONCLUSIONS: This 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis / Catepsina B / Muerte Celular / Citosol / Células Acinares Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Gastroenterology Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pancreatitis / Catepsina B / Muerte Celular / Citosol / Células Acinares Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Gastroenterology Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos