The lysine derivative aminoadipic acid, a biomarker of protein oxidation and diabetes-risk, induces production of reactive oxygen species and impairs trypsin secretion in mouse pancreatic acinar cells

Abstract

We have examined the effects of α-aminoadipic acid, an oxidized derivative from the amino acid lysine, on the physiology of mouse pancreatic acinar cells. Changes in intracellular free-Ca2+ concentration, the generation of reactive oxygen species, the levels of carbonyls and thiobarbituric-reactive substances, cellular metabolic activity and trypsin secretion were studied. Stimulation of mouse pancreatic cells with cholecystokinin (1 nM) evoked a transient increase in [Ca2+]i. In the presence of α-amoniadipic acid increases in [Ca2+]i were observed. In the presence of the compound, cholecystokinin induced a Ca2+ response that was smaller compared with that observed when cholecystokinin was applied alone. Stimulation of cells with cholecystokinin in the absence of Ca2+ in the extracellular medium abolished further mobilization of Ca2+ by α-aminoadipic acid. In addition, potential pro-oxidant conditions, reflected as increases in ROS generation, oxidation of proteins and lipids, were noted in the presence of α-aminoadipic acid. Finally, the compound impaired trypsin secretion induced by the secretagogue cholecystokinin. We conclude that the oxidized derivative from the amino acid lysine induces pro-oxidative conditions and the impairment of enzyme secretion in pancreatic acinar cells. α-aminoadipic acid thus creates a situation that could potentially lead to disorders in the physiology of the pancreas.