Thioredoxin reductase 1 is upregulated in atherosclerotic plaques: specific induction of the promoter in human macrophages by oxidized low-density lipoproteins
| Autor: | Christophe Furman, G Bricca, Mustapha Rouis, M Jaye, Anna-Klara Rundlöf, G. Larigauderie, A.-M. Kandoussi, Jean-Charles Fruchart, Corinne Copin, Elias S.J. Arnér |
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| Rok vydání: | 2003 |
| Předmět: |
Carotid Artery Diseases
Thioredoxin Reductase 1 Thioredoxin-Disulfide Reductase Molecular Sequence Data Biology Transfection Biochemistry Gene Expression Regulation Enzymologic Monocytes chemistry.chemical_compound Physiology (medical) Cell Line Tumor Humans RNA Messenger Promoter Regions Genetic chemistry.chemical_classification Endarterectomy Carotid Base Sequence Macrophages Promoter Molecular biology Reverse transcription polymerase chain reaction Lipoproteins LDL chemistry Phorbol lipids (amino acids peptides and proteins) Tumor necrosis factor alpha Selenoprotein Signal transduction |
| Zdroj: | Free radical biologymedicine. 37(1) |
| ISSN: | 0891-5849 |
| Popis: | Uptake of modified low-density lipoproteins (LDLs) by macrophages in the arterial wall is an important event in atherogenesis. Indeed, oxidatively modified LDLs (oxLDLs) are known to affect various cellular processes by modulating oxidation-sensitive signaling pathways. Here we found that the ubiquitous 55 kDa selenoprotein thioredoxin reductase 1 (TrxR1), which is a key enzyme for cellular redox control and antioxidant defense, was upregulated in human atherosclerotic plaques and expressed in foam cells. Using reverse transcription polymerase chain reaction analysis, we also found that oxLDLs, but not native LDLs (nLDLs), dose-dependently increased TrxR1 mRNA in human monocyte-derived macrophages (HMDMs). This stimulating effect was specific for oxLDLs, as pro-inflammatory factors, such as lipopolysaccharides (LPSs), interleukin-1beta (IL-1beta), interleukin-6 (Il-6), and tumor necrosis factor alpha (TNFalpha), under the same conditions, failed to induce TrxR1 mRNA levels to the same extent. Moreover, phorbol ester-differentiated THP-1 cells or HMDMs transiently transfected with TrxR1 promoter fragments linked to a luciferase reporter gene allowed identification of a defined promoter region as specifically responding to the phospholipid component of oxLDLs (p.05 vs. phospholipid component of nLDLs). Gel mobility shift analyses identified a short 40-nucleotide stretch of the promoter carrying AP-1 and HoxA5 consensus motifs that responded with an altered shift pattern in THP-1 cells treated with oxLDLs, however, without evident involvement of either the Fos, Jun, Nrf2 or HoxA5 transcription factors. |
| Databáze: | OpenAIRE |
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