{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:35:08Z","timestamp":1761057308011},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,12,25]],"date-time":"2001-12-25T00:00:00Z","timestamp":1009238400000},"content-version":"vor","delay-in-days":908,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Biochemistry"],"published-print":{"date-parts":[[1999,7]]},"abstract":"<jats:p>Recent studies have demonstrated that the protein product (natural resistance associated macrophage protein\u20032, Nramp2) encoded by the gene <jats:italic>Nramp2<\/jats:italic> acts as an Fe transporter involved in the uptake of Fe from transferrin (Tf) and low <jats:italic>M<\/jats:italic><jats:sub>r<\/jats:sub> Fe complexes. Interestingly, there are two splice variants of <jats:italic>Nramp2<\/jats:italic>, one with a putative iron\u2010responsive element (IRE) in its 3\u2032 untranslated region (UTR) and another without. Due to the importance of Nramp2 in Fe transport, and the presence of an IRE in its 3\u2032\u2010UTR, we have examined the effect of Fe\u2010deprivation, Fe\u2010loading, and nitrogen monoxide on the expression of <jats:italic>Nramp2<\/jats:italic> mRNA. These results were compared to the expression of transferrin receptor (TfR) mRNA which also has IREs in its 3\u2032\u2010UTR and is regulated by Fe and NO via the binding of iron\u2010regulatory proteins (IRPs) to its IREs. Our experiments show that the IRE in <jats:italic>Nramp2<\/jats:italic> mRNA does bind the IRPs in lysates from a mouse fibroblast cell line (LMTK<jats:sup>\u2212<\/jats:sup>). Moreover, reverse transcription\u2010PCR (RT\u2010PCR) demonstrated that both the IRE and non\u2010IRE\u2010containing transcripts were present within these cells. However, there was no change in <jats:italic>Nramp2<\/jats:italic> mRNA expression in LMTK<jats:sup>\u2212<\/jats:sup> cells after a 20\u2010h incubation with either the Fe chelator, desferrioxamine (DFO), the Fe donor, ferric ammonium citrate (FAC), or the NO generator, <jats:italic>S<\/jats:italic>\u2010nitroso\u2010<jats:italic>N<\/jats:italic>\u2010acetylpenicillamine (SNAP). In contrast, these agents caused a marked change in the RNA\u2010binding activity of the IRPs and the expression of <jats:italic>TfR<\/jats:italic> mRNA. In addition, both FAC and DFO caused an appropriate change in [<jats:sup>59<\/jats:sup>Fe] uptake from [<jats:sup>59<\/jats:sup>Fe]Tf, viz., an increase in Fe uptake after exposure to DFO and a decrease after treatment with FAC. As Nramp2 can transport Fe from non\u2010Tf\u2010bound Fe, the effect of preincubation with DFO and FAC was also examined on Fe uptake from [<jats:sup>59<\/jats:sup>Fe]nitrilotriacetate and [<jats:sup>59<\/jats:sup>Fe]citrate. However, in contrast to the results found for [<jats:sup>59<\/jats:sup>Fe]Tf, incubation with DFO and FAC did not result in appropriate regulation of Fe uptake from [<jats:sup>59<\/jats:sup>Fe]nitrilotriacetate or [<jats:sup>59<\/jats:sup>Fe]citrate. These data demonstrate that non\u2010Tf\u2010bound Fe uptake was not under control of the IRP\u2010IRE system in these cells. Collectively, the results indicate that in LMTK\u2010fibroblasts <jats:italic>Nramp2<\/jats:italic> mRNA expression was not regulated like TfR mRNA.<\/jats:p>","DOI":"10.1046\/j.1432-1327.1999.00447.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T17:26:40Z","timestamp":1047403600000},"page":"41-50","source":"Crossref","is-referenced-by-count":68,"title":["The effect of intracellular iron concentration and nitrogen monoxide on <i>Nramp2<\/i> expression and non\u2010transferrin\u2010bound iron uptake"],"prefix":"10.1111","volume":"263","author":[{"given":"S. L.","family":"Wardrop","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy.","volume":"264","author":"Grootveld M.","year":"1989","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90046-S"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-60471-3_6"},{"key":"e_1_2_6_51_2","doi-asserted-by":"crossref","first-page":"17481","DOI":"10.1016\/S0021-9258(17)32466-3","article-title":"Optimal sequence and structure of iron\u2010responsive elements. Selection of RNA stem\u2010loops with high affinity for iron\u2010regulatory factor.","volume":"269","author":"Henderson B.R.","year":"1994","journal-title":"J. Biol. 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