{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:49:15Z","timestamp":1774460955076,"version":"3.50.1"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:p>AI (anaemia of inflammation) often manifests in patients with chronic immune activation due to cancer, chronic infections, autoimmune disorders, rheumatoid arthritis and other diseases. The pathogenesis of AI is complex and involves cytokine-mediated inhibition of erythropoiesis, insufficient erythropoietin production and diminished sensitivity of erythroid progenitors to this hormone, and retention of iron in haemoglobin-processing macrophages. NO (nitric oxide) is a gaseous molecule produced by activated macrophages that has been identified as having numerous effects on iron metabolism. In the present study, we explore the possibility that NO affects iron metabolism in reticulocytes and our results suggest that NO may also contribute to AI. We treated reticulocytes with the NO donor SNP (sodium nitroprusside). The results indicate that NO inhibits haem synthesis dramatically and rapidly at the level of erythroid-specific 5-aminolaevulinic acid synthase 2, which catalyses the first step of haem synthesis in erythroid cells. We also show that NO leads to the inhibition of iron uptake via the Tf (transferrin)\u2013Tf receptor pathway. In addition, NO also causes an increase in eIF2\u03b1 (eukaryotic initiation factor 2\u03b1) phosphorylation levels and decreases globin translation. The profound impairment of haem synthesis, iron uptake and globin translation in reticulocytes by NO raises the possibility that this gas may also contribute to AI.<\/jats:p>","DOI":"10.1042\/bj20121649","type":"journal-article","created":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T14:00:08Z","timestamp":1359640808000},"page":"61-67","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nitrogen monoxide inhibits haem synthesis in mouse reticulocytes"],"prefix":"10.1042","volume":"451","author":[{"given":"Marc\u00a0R.","family":"Mikhael","sequence":"first","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 C\u00f4te Ste-Catherine Road, Montr\u00e9al, QC, Canada, H3T 1E2"},{"name":"Department of Physiology, 3655 Promenade Sir William Osler, Montr\u00e9al, QC, Canada, H3G 1Y6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Soe-Lin","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 C\u00f4te Ste-Catherine Road, Montr\u00e9al, QC, Canada, H3T 1E2"},{"name":"Department of Experimental Medicine, McGill University, Lady Meredith House, 1110 Pine Avenue West, Montr\u00e9al, QC, Canada, H3A 1A3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameer","family":"Apte","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 C\u00f4te Ste-Catherine Road, Montr\u00e9al, QC, Canada, H3T 1E2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prem","family":"Ponka","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 C\u00f4te Ste-Catherine Road, Montr\u00e9al, QC, Canada, H3T 1E2"},{"name":"Department of Physiology, 3655 Promenade Sir William Osler, Montr\u00e9al, QC, Canada, H3G 1Y6"},{"name":"Department of Experimental Medicine, McGill University, Lady Meredith House, 1110 Pine Avenue West, Montr\u00e9al, QC, Canada, H3A 1A3"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2013,3,14]]},"reference":[{"key":"2021112215313041500_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-4157(96)00014-7","article-title":"The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells","volume":"1331","author":"Richardson","year":"1997","journal-title":"Biochim. 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