TAUROURSODEOXICHOLIC ACID INCREASES AMYLASE SECRETION, REDUCES ENDOPLASMIC RETICULUM STRESS AND APOPTOSIS IN PANCREATIC ACINI

Background: The early accumulation of unfolded proteins in the Endoplasmic reticulum (ER) during acute pancreatitis initiates the unfolded protein response (UPR). The UPR is important in pancreatic development and secretagogues activate different components of the UPR that can lead to acinar damage and apoptosis. However, effects that support the ER function of protein folding are unknown. Our study aimed to examine the effects of ER-chaperone tauroursodeoxicholic acid (TUDCA) on acinar cell function and components of the UPR. Materials & Methods: Isolated rat pancreatic acini were stimulated with CCK (10 pM-10 nM). Half of the cells were preincubated in 250 μg TUDCA. UPR components, including BiP expression, PERK phosphorylation, XBP1 splicing, and caspase 3 activation, were measured, as were effects on amylase secretion. Results: TUDCA preincubation was followed by an increase of about 30% of amylase secretion. Specific Westernblotting revealed that CCK in supraphysiologic doses increased BiB levels, PERK phosphorylation, XBP1 splicing and Caspase 3 activation. All of this was significantly decreased after preincubation with TUDCA and CCK8 at 1 nM and higher (BiP minus 61%, XBP1 minus 51%, PERK minus 43% and caspase 3 minus 88%). Conclusions: The ER function and stress response appears to be involved in pancreatic physiology and pathophysiology. Preincubation with an ER-chaperone lead to an increase acinar secretion, reduced UPR elements and caspase activation. Efforts should be directed at understanding the roles of these mechanisms in the pancreas.