Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
Journal article, 2006
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.
metabolism
Reverse Transcriptase Polymerase Chain Reaction
metabolism
metabolism
Thioredoxins
genetics
Female
Humans
Up-Regulation
genetics
Middle Aged
Oxidation-Reduction
Pentose Phosphate Pathway
genetics
Lipoproteins
metabolism
Male
Oligonucleotide Array Sequence Analysis
Oxidative Stress
Atherosclerosis
LDL
Macrophages
pharmacology
Glutathione
Gene Expression
Author
Daniel Hägg
University of Gothenburg
Mikael Englund
University of Gothenburg
Margareta Jernås
University of Gothenburg
Caroline Schmidt
University of Gothenburg
Olov Wiklund
University of Gothenburg
Lillemor Mattsson Hultén
University of Gothenburg
Bertil Ohlsson
University of Gothenburg
Lena M S Carlsson
University of Gothenburg
Björn Carlsson
University of Gothenburg
Per-Arne Svensson
University of Gothenburg
Atherosclerosis
0021-9150 (ISSN) 18791484 (eISSN)
Vol. 185 2 282-9Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1016/j.atherosclerosis.2005.06.034
PubMed
16046214