{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T20:07:52Z","timestamp":1786997272195,"version":"build-2736575974"},"reference-count":52,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["CA16087"],"award-info":[{"award-number":["CA16087"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2006,6]]},"DOI":"10.1016\/j.taap.2005.11.006","type":"journal-article","created":{"date-parts":[[2006,1,5]],"date-time":"2006-01-05T08:25:35Z","timestamp":1136449535000},"page":"245-255","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":81,"title":["Effects of 12 metal ions on iron regulatory protein 1 (IRP-1) and hypoxia-inducible factor-1 alpha (HIF-1\u03b1) and HIF-regulated genes"],"prefix":"10.1016","volume":"213","author":[{"given":"Qin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2005.11.006_bib1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1023\/A:1020723117584","article-title":"Copper exposure and potential biomarkers of copper metabolism","volume":"16","author":"Araya","year":"2003","journal-title":"Biometals"},{"key":"10.1016\/j.taap.2005.11.006_bib2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.toxlet.2005.01.005","article-title":"Metallothionein overexpression and resistance to toxic stress","volume":"157","author":"Beattie","year":"2005","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.taap.2005.11.006_bib3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.taap.2004.11.011","article-title":"Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells","author":"Chen","year":"2005","journal-title":"Toxicol. Appl."},{"key":"10.1016\/j.taap.2005.11.006_bib4","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1006\/bbrc.2000.2180","article-title":"Zinc induces the accumulation of hypoxia-inducible factor (HIF)-1alpha, but inhibits the nuclear translocation of HIF-1beta, causing HIF-1 inactivation","volume":"268","author":"Chun","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.taap.2005.11.006_bib5","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1073\/pnas.89.10.4554","article-title":"Modulation of the RNA-binding activity of a regulatory protein by iron in vitro: switching between enzymatic and genetic function?","volume":"89","author":"Constable","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.taap.2005.11.006_bib6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mrfmmm.2005.06.008","article-title":"Nickel carcinogenesis: epigenetics and hypoxia signaling","volume":"592","author":"Costa","year":"2005","journal-title":"Mutat. Res."},{"key":"10.1016\/j.taap.2005.11.006_bib7","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1124\/mol.64.6.1485","article-title":"Hypoxia inducible factor-1 alpha-independent suppression of aryl hydrocarbon receptor-regulated genes by nickel","volume":"64","author":"Davidson","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.taap.2005.11.006_bib8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/00039896.1995.9940887","article-title":"Symptom clusters in a community with chronic exposure to chemicals in two superfund sites","volume":"50","author":"Dayal","year":"1995","journal-title":"Arch. Environ. Health"},{"key":"10.1016\/j.taap.2005.11.006_bib9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxlet.2004.02.018","article-title":"Heavy metals (Ni, Cr, Cu) in the Karoon waterway river, Iran","volume":"151","author":"Diagomanolin","year":"2004","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.taap.2005.11.006_bib10","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1093\/carcin\/19.8.1401","article-title":"Effects of Cr(VI) on the expression of the oxidative stress genes in human lung cells","volume":"19","author":"Dubrovskaya","year":"1998","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.taap.2005.11.006_bib11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1006\/abbi.1997.9892","article-title":"Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos","volume":"340","author":"Fang","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.taap.2005.11.006_bib12","doi-asserted-by":"crossref","first-page":"31963","DOI":"10.1074\/jbc.M200082200","article-title":"Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase\/Akt pathway and reactive oxygen species","volume":"277","author":"Gao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2005.11.006_bib13","doi-asserted-by":"crossref","first-page":"45041","DOI":"10.1074\/jbc.M202775200","article-title":"p38 signaling-mediated hypoxia-inducible factor 1alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells","volume":"277","author":"Gao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2005.11.006_bib14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1023\/B:MCBI.0000007259.65742.16","article-title":"Arsenite induces HIF-1alpha and VEGF through PI3K, Akt and reactive oxygen species in DU145 human prostate carcinoma cells","volume":"255","author":"Gao","year":"2004","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.taap.2005.11.006_bib15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1021\/cr020620d","article-title":"Metallothioneins: zinc, cadmium, mercury, and copper thiolates and selenolates mimicking protein active site features-structural aspects and biological implications","volume":"104","author":"Henkel","year":"2004","journal-title":"Chem. Rev."},{"key":"10.1016\/j.taap.2005.11.006_bib16","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1096\/fj.04-3399fje","article-title":"Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway","volume":"19","author":"Hirsila","year":"2005","journal-title":"FASEB J."},{"key":"10.1016\/j.taap.2005.11.006_bib17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s002040050352","article-title":"Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys","volume":"71","author":"Horiguchi","year":"1996","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.taap.2005.11.006_bib18","doi-asserted-by":"crossref","first-page":"27874","DOI":"10.1074\/jbc.M002185200","article-title":"Induction of vascular endothelial growth factor in human astrocytes by lead. Involvement of a protein kinase C\/activator protein-1 complex-dependent and hypoxia-inducible factor 1-independent signaling pathway","volume":"275","author":"Hossain","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2005.11.006_bib19","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/carcin\/bgh253","article-title":"AMP-activated protein kinase activity is required for vanadate-induced hypoxia-inducible factor 1alpha expression in DU145 cells","volume":"25","author":"Hwang","year":"2004","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.taap.2005.11.006_bib20","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.taap.2005.11.006_bib21","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"Jaakkola","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.taap.2005.11.006_bib22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbrc.2005.05.083","article-title":"Cadmium induces a novel metallothionein and phytochelatin 2 in an aquatic fungus","volume":"333","author":"Jaeckel","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.taap.2005.11.006_bib23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0300-483X(88)90055-8","article-title":"Ferritin: an expanded role in metabolic regulation","volume":"48","author":"Joshi","year":"1988","journal-title":"Toxicology"},{"key":"10.1016\/j.taap.2005.11.006_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(03)02457-0","article-title":"Alterations in cellular IRP-dependent iron regulation by in vitro manganese exposure in undifferentiated PC12 cells","volume":"973","author":"Kwik-Uribe","year":"2003","journal-title":"Brain Res."},{"key":"10.1016\/j.taap.2005.11.006_bib25","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1158\/0008-5472.CAN-03-0737","article-title":"Nickel compounds act through phosphatidylinositol-3-kinase\/Akt-dependent, p70(S6k)-independent pathway to induce hypoxia inducible factor transactivation and Cap43 expression in mouse epidermal Cl41 cells","volume":"64","author":"Li","year":"2004","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2005.11.006_bib26","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.jinorgbio.2004.04.011","article-title":"Zinc and cadmium specifically interfere with RNA-binding activity of human iron regulatory protein 1","volume":"98","author":"Martelli","year":"2004","journal-title":"J. Inorg. Biochem."},{"key":"10.1016\/j.taap.2005.11.006_bib27","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1182\/blood-2004-10-3980","article-title":"Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation","volume":"105","author":"Martin","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.taap.2005.11.006_bib28","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1006\/bcmd.2002.0578","article-title":"Mechanisms and regulation of intestinal iron absorption","volume":"29","author":"Morgan","year":"2002","journal-title":"Blood Cells Mol. Diseases"},{"key":"10.1016\/j.taap.2005.11.006_bib29","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/oxfordjournals.jbchem.a021914","article-title":"Aluminum taken up by transferrin-independent iron uptake affects the iron metabolism in rat cortical cells","volume":"123","author":"Oshiro","year":"1998","journal-title":"J. Biochem. (Tokyo)"},{"key":"10.1016\/j.taap.2005.11.006_bib30","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/bbrc.2001.6182","article-title":"Modulation of iron regulatory protein-1 by various metals","volume":"290","author":"Oshiro","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.taap.2005.11.006_bib31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0167-4889(99)00056-7","article-title":"Differential expression of the RTP\/Drg1\/Ndr1 gene product in proliferating and growth arrested cells","volume":"1450","author":"Piquemal","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.taap.2005.11.006_bib32","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.tiv.2005.01.001","article-title":"Comparison of the sensitivity of three lung derived cell lines to metals from combustion derived particulate matter","volume":"19","author":"Riley","year":"2005","journal-title":"Toxicol. In Vitro"},{"key":"10.1016\/j.taap.2005.11.006_bib33","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/annhyg\/meh029","article-title":"Dermal exposure to electroplating fluids and metalworking fluids in the UK","volume":"48","author":"Roff","year":"2004","journal-title":"Ann. Occup. Hyg."},{"key":"10.1016\/j.taap.2005.11.006_bib34","doi-asserted-by":"crossref","first-page":"20055","DOI":"10.1074\/jbc.272.32.20055","article-title":"Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1","volume":"272","author":"Rolfs","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2005.11.006_bib35","first-page":"3375","article-title":"Carcinogenic metals induce hypoxia-inducible factor-stimulated transcription by reactive oxygen species-independent mechanism","volume":"60","author":"Salnikow","year":"2000","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2005.11.006_bib36","first-page":"3524","article-title":"The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis","volume":"63","author":"Salnikow","year":"2003","journal-title":"Cancer Res."},{"key":"10.1016\/j.taap.2005.11.006_bib37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1620\/tjem.196.9","article-title":"Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals","volume":"196","author":"Sato","year":"2002","journal-title":"Tohoku J. Exp. Med."},{"key":"10.1016\/j.taap.2005.11.006_bib38","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev.cellbio.15.1.551","article-title":"Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1","volume":"15","author":"Semenza","year":"1999","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1016\/j.taap.2005.11.006_bib39","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1023\/B:MCBI.0000007257.67733.3b","article-title":"Arsenite induces p70S6K1 activation and HIF-1alpha expression in prostate cancer cells","volume":"255","author":"Skinner","year":"2004","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.taap.2005.11.006_bib40","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0304-4165(02)00497-X","article-title":"Genetic regulation of cell function in response to iron overload or chelation","volume":"1619","author":"Templeton","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.taap.2005.11.006_bib41","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.aquatox.2004.06.002","article-title":"Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in rainbow trout (Oncorhynchus mykiss)","volume":"69","author":"van Heerden","year":"2004","journal-title":"Aquat. Toxicol."},{"key":"10.1016\/j.taap.2005.11.006_bib42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1574-6976.2002.tb00609.x","article-title":"The role of iron in Campylobacter gene regulation, metabolism and oxidative stress defense","volume":"26","author":"van Vliet","year":"2002","journal-title":"FEMS Microbiol. Rev."},{"key":"10.1016\/j.taap.2005.11.006_bib43","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/jbm.10384","article-title":"Cytotoxicity of ingredients of various dental materials and related compounds in L2- and A549 cells","volume":"63","author":"Walther","year":"2002","journal-title":"J. Biomed. Mater. Res."},{"key":"10.1016\/j.taap.2005.11.006_bib44","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1182\/blood.V82.12.3610.3610","article-title":"Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction","volume":"82","author":"Wang","year":"1993","journal-title":"Blood"},{"key":"10.1016\/j.taap.2005.11.006_bib45","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix\u2013loop\u2013helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"Wang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.taap.2005.11.006_bib46","first-page":"L987","article-title":"Iron uptake and Nramp2\/DMT1\/DCT1 in human bronchial epithelial cells","volume":"282","author":"Wang","year":"2002","journal-title":"Am. J. Physiol.: Lung Cell. Mol. Physiol."},{"key":"10.1016\/j.taap.2005.11.006_bib47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0162-0134(01)00308-7","article-title":"Aluminium toxicity and iron homeostasis","volume":"87","author":"Ward","year":"2001","journal-title":"J. Inorg. Biochem."},{"key":"10.1016\/j.taap.2005.11.006_bib48","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1096\/fj.01-0944rev","article-title":"Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression","volume":"16","author":"Wenger","year":"2002","journal-title":"FASEB J."},{"key":"10.1016\/j.taap.2005.11.006_bib49","doi-asserted-by":"crossref","first-page":"15911","DOI":"10.1074\/jbc.M300463200","article-title":"Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel\u2013Lindau protein by direct binding to hypoxia-inducible factor-alpha","volume":"278","author":"Yuan","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.taap.2005.11.006_bib50","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.taap.2003.08.011","article-title":"Nickel-induced down-regulation of serpin by hypoxic signaling","volume":"194","author":"Zhao","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2005.11.006_bib51","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0006-8993(01)02049-2","article-title":"Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells","volume":"897","author":"Zheng","year":"2001","journal-title":"Brain Res."},{"key":"10.1016\/j.taap.2005.11.006_bib52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0006-8993(99)01558-9","article-title":"Alteration of iron homeostasis following chronic exposure to manganese in rats","volume":"833","author":"Zheng","year":"1999","journal-title":"Brain Res."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X0500640X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X0500640X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T20:36:54Z","timestamp":1758573414000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X0500640X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,6]]}},"alternative-id":["S0041008X0500640X"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2005.11.006","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2006,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effects of 12 metal ions on iron regulatory protein 1 (IRP-1) and hypoxia-inducible factor-1 alpha (HIF-1\u03b1) and HIF-regulated genes","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2005.11.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2005 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}