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.
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.
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.