Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis.
Zn homeostasis in animals is a consequence of avid uptake and retention, except during conditions of limited dietary availability, and/or factors such as parasites, which compete for this micronutrient or compromise retention by the host. Membrane proteins that facilitate Zn transport constitute the SLC30A (ZnT) and SLC39A (Zip) gene families. Because dietary recommendations are based on the balance between intestinal absorption and endogenous losses, we have studied Zn transporter expression of the murine intestinal-pancreatic axis to identify transporters that are likely to be involved in homeostatic control of Zn metabolism. Marked tissue specificity of expression was observed in Zn-depleted vs. Zn-adequate mice. As shown by quantitative PCR, Western blot analysis, and immunohistochemistry, intestinal Zip4 was markedly up-regulated in response to Zn-depletion conditions. The increased abundance of Zip4 is concentrated at the apical membrane of enterocytes. There are 16 ZnT and Zip transporters expressed in pancreas. Only two, ZnT1 and ZnT2 (both cellular Zn exporters), show a progressive down-regulation under Zn-depleted conditions. In Zn-adequate mice, ZnT1 is diffusely distributed in acinar cell cytoplasm and colocalizes with alpha-amylase but is not detected in pancreatic islets. In acinar cells during Zn depletion, ZnT1 is localized to the plasma membrane. Intestinal Zip4 up-regulation by Zn-depletion conditions is dampened in metallothionein knockout mice, suggesting that intracellular Zn pools influence these responses. The results show that Zn transporter expression in the intestinal-pancreatic axis is a component of the homeostatic regulation of this micronutrient.
Liuzzi
Juan P
JP
Nutritional Genomics Laboratory, Center for Nutritional Sciences, and Small Animal Clinical Sciences Department, University of Florida, Gainesville, FL 32611, USA.
Bobo
Jeffrey A
JA
Lichten
Louis A
LA
Samuelson
Don A
DA
Cousins
Robert J
RJ
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D005810:Multigene Family; D010179:Pancreas / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D012333:RNA, Messenger; C017800:zinc-binding protein; D015032:Zinc