Thioredoxin reductase 1 is upregulated in atherosclerotic plaques:: Specific induction of the promoter in human macrophages by oxidized low-density lipoproteins

被引:40
作者
Furman, C
Rundlöf, AK
Larigauderie, G
Jaye, M
Bricca, G
Copin, C
Kandoussi, AM
Fruchart, JC
Arnér, ESJ
Rouis, M
机构
[1] Inst Pasteur, F-59019 Lille, France
[2] INSERM, U545, F-59019 Lille, France
[3] Karolinska Inst, Dept Med Biochem & Biophys, Med Nobel Inst Biochem, SE-17177 Stockholm, Sweden
[4] Fac Med Rene Laennec, INSERM, U331, F-69372 Lyon, France
关键词
D O I
10.1016/j.freeradbiomed.2004.04.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (1L-6), and turner 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. (C) 2004 Elsevier Inc. All rights reserved.
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页码:71 / 85
页数:15
相关论文
共 79 条
[1]  
Alissa EM, 2003, MED SCI MONITOR, V9, pRA9
[2]  
AMER ESJ, 2000, EUR J BIOCHEM, V267, P6102, DOI DOI 10.1046/J.1432-1327.2000.01701.X.PMID:11012661
[3]   NK-lysin, a disulfide-containing effector peptide of T-lymphocytes, is reduced and inactivated by human thioredoxin reductase - Implication for a protective mechanism against NK-lysin cytotoxicity [J].
Andersson, M ;
Holmgren, A ;
Spyrou, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (17) :10116-10120
[4]   Thioredoxin reductase is the major selenoprotein expressed in human umbilical-vein endothelial cells and is regulated by protein kinase C [J].
Anema, SM ;
Walker, SW ;
Howie, AF ;
Arthur, JR ;
Nicol, F ;
Beckett, GJ .
BIOCHEMICAL JOURNAL, 1999, 342 :111-117
[5]  
Arner ESJ, 1999, METHOD ENZYMOL, V300, P226
[6]   Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase [J].
Arner, ESJ ;
Nordberg, J ;
Holmgren, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 225 (01) :268-274
[7]   Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis [J].
Barbier, O ;
Torra, IP ;
Duguay, Y ;
Blanquart, C ;
Fruchart, JC ;
Glineur, C ;
Staels, B .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (05) :717-726
[8]  
BASHEERUDDIN K, 1992, J BIOL CHEM, V267, P1219
[9]   Thioredoxin reductase as a pathophysiological factor and drug target [J].
Becker, K ;
Gromer, S ;
Schirmer, RH ;
Müller, S .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (20) :6118-6125
[10]   HUMAN THIOREDOXIN REDUCTASE DIRECTLY REDUCES LIPID HYDROPEROXIDES BY NADPH AND SELENOCYSTINE STRONGLY STIMULATES THE REACTION VIA CATALYTICALLY GENERATED SELENOLS [J].
BJORNSTEDT, M ;
HAMBERG, M ;
KUMAR, S ;
XUE, J ;
HOLMGREN, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (20) :11761-11764