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Increasing concentrations of iron in the culture medium elicited increasing amounts of intracellular iron and of the reactive iron pool. The cells had both IRP1 and IRP2 activities, being IRP1 activity quantitatively predominant. When iron in the culture medium increased from 1 to 40\u2003\u00b5<jats:sc>m<\/jats:sc>, IRP2 activity decreased to nil. In contrast, IRP1 activity decreased when iron increased up to 20\u2003\u00b5<jats:sc>m<\/jats:sc>, and then, unexpectedly, increased. IRP1 activity at iron concentrations above 20\u2003\u00b5<jats:sc>m<\/jats:sc>was functional as it correlated with increased<jats:sup>55<\/jats:sup>Fe uptake. The increase in IRP1 activity was mediated by oxidative\u2010stress as it was largely abolished by<jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine. Culturing cells with iron resulted in proteins and DNA modifications. In summary, iron uptake by N2A cells and hippocampus neurons did not shut off at high iron concentrations in the culture media. As a consequence, iron accumulated and generated oxidative damage. This behavior is probably a consequence of the paradoxical activation of IRP1 at high iron concentrations, a condition that may underlie some processes associated with neuronal degeneration and death.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2002.00971.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T07:01:39Z","timestamp":1047452499000},"page":"240-248","source":"Crossref","is-referenced-by-count":43,"title":["An oxidative stress\u2010mediated positive\u2010feedback iron uptake loop in neuronal cells"],"prefix":"10.1111","volume":"82","author":[{"given":"Claudia","family":"N\u00fa\u00f1ez\u2010Millacura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Tapia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo B.","family":"Maccioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco T.","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,7,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0578fje"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1997.273.2.G275"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(77)90594-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.1.514"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100245200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4406"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00012-X"},{"key":"e_1_2_7_9_1","first-page":"2812","article-title":"Effect of inhibitors of ornithine decarboxylase on the differentiation of mouse neuroblastoma cells","volume":"43","author":"Chen K. 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