Down-Regulation of the Expression of the FIH-1 and ARD-1 Genes at the Transcriptional Level by Nickel and Cobalt in the Human Lung Adenocarcinoma A549 Cell Line
| Autor: | Max Costa, Qingdong Ke, Thomas Kluz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Hypoxia-Inducible Factor 1
Lung Neoplasms Health Toxicology and Mutagenesis Protein subunit ARD-1 Repressor Down-Regulation lcsh:Medicine FIH-1 Biology Adenocarcinoma Article Mixed Function Oxygenases nickel Transcription (biology) cobalt hypoxia HIF-1a Acetyltransferases Cell Line Tumor Humans N-Terminal Acetyltransferase E RNA Messenger Gene Transcription factor N-Terminal Acetyltransferase A Regulation of gene expression lcsh:R Public Health Environmental and Occupational Health Hypoxia-Inducible Factor 1 alpha Subunit Repressor Proteins Biochemistry Gene Expression Regulation Acetyltransferase Transcription Factors |
| Zdroj: | International Journal of Environmental Research and Public Health, Vol 2, Iss 1, Pp 10-13 (2005) International Journal of Environmental Research and Public Health International Journal of Environmental Research and Public Health; Volume 2; Issue 1; Pages: 10-13 |
| ISSN: | 1660-4601 |
| Popis: | Although nickel and cobalt compounds have been known to cause induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) and activation of a battery of hypoxia-inducible genes in the cell, the molecular mechanisms of this induction remain unclear. The post-translational modification of HIF-1a, the oxygen-sensitive subunit of HIF-1, regulates stabilization, nuclear translocation, DNA binding activity, and transcriptional activity of the protein. Among the enzymes regulating the post-translational modification of HIF-la, the factor inhibiting HIF-1 (FIH-1) hydroxylates the protein at asparagine 803, suppressing the interaction of HIF-1a with transcription coactivators p300/CBP and reducing the transcriptional activity of the protein. ARD-1, the acetyltransferase, acetylates HIF-1a at lysine 532, which enhances the interaction of HIF-1a with pVHL. Therefore, FIH-1 and ARD-1 negatively regulate the transcriptional activity and the stability of HIF-1a. We examined the mRNA levels of FIH-l and ARD-1 genes after exposure nickel (II) or cobalt (II) to the cell and found that both genes were down-regulated by the chemical treatment, which may lead to reduced levels of both proteins and result in increased level of HIF-1 a and its transcriptional activity. |
| Databáze: | OpenAIRE |
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