Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
Artikel i vetenskaplig tidskrift, 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
Författare
Daniel Hägg
Göteborgs universitet
Mikael Englund
Göteborgs universitet
Margareta Jernås
Göteborgs universitet
Caroline Schmidt
Göteborgs universitet
Olov Wiklund
Göteborgs universitet
Lillemor Mattsson Hultén
Göteborgs universitet
Bertil Ohlsson
Göteborgs universitet
Lena M S Carlsson
Göteborgs universitet
Björn Carlsson
Göteborgs universitet
Per-Arne Svensson
Göteborgs universitet
Atherosclerosis
0021-9150 (ISSN) 18791484 (eISSN)
Vol. 185 2 282-9Ämneskategorier
MEDICIN OCH HÄLSOVETENSKAP
DOI
10.1016/j.atherosclerosis.2005.06.034
PubMed
16046214