Abstract：
:Long-term exposure of rats to cadmium (Cd) resulted in a marked suppression of erythropoietin (Epo) mRNA expression in the kidneys and the development of severe anemia. A recent report revealed that Cd inhibited hypoxia-inducible factor 1 (HIF-1) binding activity and Epo mRNA expression and protein production. However, Epo gene expression is also regulated by transcription factor GATA-2, which binds to the GATA binding site of the Epo promoter. To elucidate the mechanism of suppression of Epo by Cd, the effect of Cd on GATA-2 function was studied. Epo promoter/enhancer luciferase constructs, one with the wild-type promoter and another with a promoter with a mutant GATA site, were transfected into Hep3B cells. No significant difference in Epo promoter activity in these two types of cells was observed in the presence of Cd. The binding activity of GATA-2 was not affected by Cd. This study showed that Cd inhibited HIF-1 binding activity and Epo promoter activity, and then suppressed Epo protein production. Inhibition of Epo gene expression by Cd depends on suppression of HIF-1 binding activity, not on alteration of GATA function.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Obara N,Imagawa S,Nakano Y,Suzuki N,Yamamoto M,Nagasawa Tdoi
10.1007/s00204-003-0444-0keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
267-73issue
5eissn
0340-5761issn
1432-0738journal_volume
77pub_type
杂志文章abstract：:The aim was to study the long-term response in the olfactory mucosa of NMRI mice after exposure to the olfactory toxicants dichlobenil (a herbicide) or methimazole (an antithyroid drug). Three and six months after exposure to dichlobenil (2x or 1 x 25 mg/kg i.p.), the dorsomedial part of the olfactory region showed a ...
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pub_type： 杂志文章,评审
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：2015-02-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00296900
更新日期：1979-02-23 00:00:00
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pub_type： 杂志文章
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更新日期：2019-07-01 00:00:00
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journal_title：Archives of toxicology
pub_type：
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