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Effect of cadmium on heme oxygenase‐1 during cellular iron deficiency
Author(s) -
Lai Chengzhi,
Loo George
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.921.12
Subject(s) - heme oxygenase , chemistry , cadmium , ferrous , deferoxamine , dmt1 , nadph oxidase , heme , biochemistry , enzyme , transporter , gene , organic chemistry
Trace metals can have contrasting biological effects. Iron and cadmium are normally regarded as a crucial micronutrient and noxious environmental agent, respectively. However, it is unknown if iron is required to help defend cells against cadmium. Thus, the effect of cadmium on cytoprotective heme oxygenase‐1 (HO‐1) during cellular iron deficiency caused by iron chelators (deferoxamine and 2,2′‐dipyridyl) was investigated in HCT‐116 cells. Exposing cells to cadmium induced HO‐1 enzyme activity and increased HO‐1 protein expression, which were attenuated by thiol antioxidants and also by chemical inhibitors of the flavoheme protein, NADPH oxidase (NOX). In iron‐deficient cells exposed to cadmium, induction of HO‐1 mRNA, protein, and enzyme activity were all blunted. Also, nuclear translocation of the redox‐sensitive transcription factor, Nrf2, which is known to activate the HO‐1 gene, was diminished. But, after treating the iron‐deficient cells with ferrous sulfate to restore positive iron balance, all of the above molecular events were not impaired upon exposing the rescued cells to cadmium. Zinc or copper treatment was ineffective. These results suggest that iron, being a critical element of the NOX catalytic subunit, plays a pivotal indirect role in the capacity of cadmium and potentially other xenobiotics to optimally upregulate HO‐1 gene expression. Supported by NRI USDA CSREES (2006‐35200‐16578).