Pancreatic acinar AR42J cells differentially express ZnT1 (Slc30a1) and ZnT2 (Slc30a2) in response to zinc and glucocorticoid hormone

Abstract

Zinc homeostasis is achieved by balancing between intestinal absorption and endogenous loss. We have found that regulation of ZnT1 and ZnT2 in pancreatic acinar cells is responsive to dietary Zn intake and could be a key factor that could facilitate endogenous zinc loss via pancreatic exocrine secretions. The mechanisms of ZnT1- and ZnT2-mediated zinc efflux in pancreatic acinar cell secretions have not been characterized. First, we measured transcript abundances of the SLC30A (ZnT) zinc transporter family in human pancreatic RNA by QRT-PCR. ZnT1 and ZnT2 were shown to have the highest relative expression. Then, we used rat pancreatic AR42J cells to study the mechanisms of ZnT1- and ZnT2-mediated zinc release. We have found ZnT1 was tightly regulated by cellular zinc, as addition of exogenous zinc stimulated expression in a dose- and time-dependent manner with ZnT1 localization to the plasma membrane. In contrast, ZnT2 is localized to vesicles and expression was strongly up-regulated during AR42J cell differentiation towards the exocrine acinar cell phenotype upon induction by dexamethasone, suggesting ZnT2 functions through the exocytotic pathway, and is concomitant with digestive enzyme release. In conclusion, ZnT1 and ZnT2 may mediate endogenous Zn loss through two different pathways within pancreatic acinar AR42J cells. Supported by NIH Grant DK 31127 and Boston Family Endowment funds.