| First Author | Shawki A | Year | 2016 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 311 |
| Issue | 3 | Pages | G423-30 |
| PubMed ID | 27390324 | Mgi Jnum | J:240130 |
| Mgi Id | MGI:5882458 | Doi | 10.1152/ajpgi.00167.2016 |
| Citation | Shawki A, et al. (2016) Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse. Am J Physiol Gastrointest Liver Physiol 311(3):G423-30 |
| abstractText | 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 of (59)Fe 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. |
