Suppression of erythropoietin gene expression by cadmium depends on inhibition of HIF-1, not stimulation of GATA-2.
作者： Naoshi Obara , Shigehiko Imagawa , Yoko Nakano , Norio Suzuki , Masayuki Yamamoto
DOI: 10.1007/S00204-003-0444-0
关键词: Molecular biology 、 Binding site 、 Transfection 、 Transcriptional regulation 、 Transcription factor 、 Gene expression 、 Luciferase 、 Enhancer 、 Erythropoietin 、 Biology
摘要: Long-term exposure of rats to cadmium (Cd) resulted in a marked suppression erythropoietin (Epo) mRNA expression the kidneys and development severe anemia. A recent report revealed that Cd inhibited hypoxia-inducible factor 1 (HIF-1) binding activity Epo protein production. However, gene is also regulated by transcription GATA-2, which binds GATA site promoter. To elucidate mechanism Cd, effect on GATA-2 function was studied. promoter/enhancer luciferase constructs, one with wild-type promoter another mutant site, were transfected into Hep3B cells. No significant difference these two types cells observed presence Cd. The not affected This study showed HIF-1 activity, then suppressed Inhibition depends alteration function.
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