Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse
| Autor: | Sarah R. Anthony, Gary E. Shull, Roger T. Worrell, Melinda A. Engevik, Patrick B. Knight, Ali Shawki, Bryan Mackenzie, Robert Kim, Rusty A. Baik |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Sodium-Hydrogen Exchangers Brush border Physiology Iron absorption Sodium Iron Xenopus Water-Electrolyte Imbalance chemistry.chemical_element Nutrient Sensing Nutrition and Metabolism Biology 03 medical and health sciences Mice 0302 clinical medicine Iron homeostasis Physiology (medical) medicine Animals Humans Intestinal Mucosa Mice Knockout Hepatology Microvilli Sodium-Hydrogen Exchanger 3 Gastroenterology Biological Transport Iron deficiency medicine.disease Cell biology Sodium–hydrogen antiporter 030104 developmental biology Biochemistry chemistry Gene Expression Regulation Hereditary hemochromatosis Oocytes Whole body 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 311(3) |
| ISSN: | 1522-1547 |
| Popis: | Divalent metal-ion transporter-1 (DMT1), the principal mechanism by which nonheme iron is taken up at the intestinal brush border, is energized by the H+-electrochemical potential gradient. The provenance of the H+gradient in vivo is unknown, so we have explored a role for brush-border Na+/H+exchanger (NHE) isoforms by examining iron homeostasis and intestinal iron handling in mice lacking NHE2 or NHE3. We observed modestly depleted liver iron stores in NHE2-null (NHE2−/−) mice stressed on a low-iron diet but no change in hematological or blood iron variables or the expression of genes associated with iron metabolism compared with wild-type mice. Ablation of NHE3 strongly depleted liver iron stores, regardless of diet. We observed decreases in blood iron variables but no overt anemia in NHE3-null (NHE3−/−) mice on a low-iron diet. Intestinal expression of DMT1, the apical surface ferrireductase cytochrome b reductase-1, and the basolateral iron exporter ferroportin was upregulated in NHE3−/−mice, and expression of liver Hamp1 (hepcidin) was suppressed compared with wild-type mice. Absorption of59Fe from an oral dose was substantially impaired in NHE3−/−compared with wild-type mice. Our data point to an important role for NHE3 in generating the H+gradient that drives DMT1-mediated iron uptake at the intestinal brush border. |
| Databáze: | OpenAIRE |
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