Amino acid transporters expression in acinar cells is changed during acute pancreatitis |
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Authors: | Ilse Rooman Christian Lutz Andreia V. Pinho Katja Huggel Theresia Reding Tony Lahoutte François Verrey Rolf Graf Simone M.R. Camargo |
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Affiliation: | 1. Cancer Research Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst-Sydney, NSW, Australia;2. St Vincent''s Clinical School, University New South Wales, Australia;3. Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium;4. Institute of Physiology and ZIHP, University of Zurich, Zurich, Switzerland;5. Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain;6. Department of Surgery, University Hospital Zurich, Zurich, Switzerland;7. ICMI, Vrije Universiteit Brussel, Brussels, Belgium |
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Abstract: | Pancreatic acinar cells accumulate amino acids against a marked concentration gradient to synthesize digestive enzymes. Thus, the function of acinar cells depends on amino acid uptake mediated by active transport. Despite the importance of this process, pancreatic amino acid transporter expression and cellular localization is still unclear. We screened mouse pancreas for the expression of genes encoding amino acid transporters. We showed that the most highly expressed transporters, namely sodium dependent SNAT3 (Slc38a3) and SNAT5 (Slc38a5) and sodium independent neutral amino acids transporters LAT1 (Slc7a5) and LAT2 (Slc7a8), are expressed in the basolateral membrane of acinar cells. SNAT3 and SNAT5, LAT1 and LAT2 are expressed in acinar cells. Additional evidence that these transporters are expressed in mature acinar cells was gained using acinar cell culture and acute pancreatitis models. In the acute phase of pancreatic injury, when acinar cell loss occurs, and in an acinar cell culture model, which mimics changes occurring during pancreatitis, SNAT3 and SNAT5 are strongly down-regulated. LAT1 and LAT2 were down-regulated only in the in vitro model. At protein level, SNAT3 and SNAT5 expression was also reduced during pancreatitis. Expression of other amino acid transporters was also modified in both models of pancreatitis. The subset of transporters with differential expression patterns during acute pancreatitis might be involved in the injury/regeneration phases. Further expression, localization and functional studies will follow to better understand changes occurring during acute pancreatitis. These findings provide insight into pancreatic amino acid transport in healthy pancreas and during acute pancreatitis injury. |
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Keywords: | Acinar cells Exocrine pancreas SNAT3 SNAT5 Solute carrier families |
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