{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:47:12Z","timestamp":1761058032995,"version":"3.30.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6056,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Nitric oxide (NO) donors S\u2013nitroso\u2013N\u2013acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) modulate iron regulatory protein (IRP) activity and may, therefore, affect iron uptake through transferrin receptor expression. However, iron also enters the cell as nontransferrin\u2013bound iron (NTBI), and the aim of this study was to evaluate the effects of NO donors on NTBI transport in HepG2 cells, a model of liver physiology. Incubation with SNP and SNAP led to a time\u2013 and concentration\u2013dependent reduction in Fe<jats:sup>3+<\/jats:sup> and Fe<jats:sup>2+<\/jats:sup> uptake, thus indicating an effect on the transporter rather than on the reductase. In terms of Fe<jats:sup>2+<\/jats:sup> uptake, no variations in the Michaelis\u2013Menten constant (<jats:italic toggle=\"yes\">K<\/jats:italic>\n                                 <jats:sub>m<\/jats:sub> ) and a reduction in maximum uptake (<jats:italic toggle=\"yes\">V<\/jats:italic>\n                                 <jats:sub>max<\/jats:sub> ) (50, 33, and 16.6 fmol\/\u03bcg protein\/min in control, SNP\u2013, and SNAP\u2013treated cells, respectively) were detected, which suggested a decrease in the number of putative NTBI transport protein(s). Gel shift assays showed that IRP activity was reduced by SNP and slightly increased by SNAP. Northern blot analysis of transferrin receptor messenger RNA (mRNA) levels showed variations similar to those observed for IRPs, but both NO donors increased L\u2013ferritin mRNA levels and had no effect on the stimulator of Fe transport (SFT) mRNA. In conclusion, NO donors significantly reduce NTBI transport in HepG2 cells, an effect that seems to be IRP and SFT independent. Moreover, the reduction in NTBI uptake after NO treatment suggests that this form of iron may play a minor role in the increased hepatic iron stores observed in inflammation or that other liver cells are more involved in this pathological condition.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510290205","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:39:45Z","timestamp":1090971585000},"page":"464-470","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["Nitric Oxide Reduces Nontransferrin\u2013Bound Iron Transport in Hepg2 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