Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P < 0.05) and catalase (P < 0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
Hägg
Daniel
D
Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita stråket 15, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. daniel.hagg@medic.gu.se
Englund
Mikael C O
MC
Jernås
Margareta
M
Schmidt
Caroline
C
Wiklund
Olov
O
Hultén
Lillemor Mattsson
LM
Ohlsson
Bertil G
BG
Carlsson
Lena M S
LM
Carlsson
Björn
B
Svensson
Per-Arne
PA
D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013879:Thioredoxins; D005978:Glutathione