Functions of coenzyme Q10 in inflammation and gene expression.
Clinical studies demonstrated the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapeutic in cardiovascular diseases, mitochondrial myopathies and neurodegenerative diseases. More recently, expression profiling revealed that Coenzyme Q10 (CoQ10) influences the expression of several hundred genes. To unravel the functional connections of these genes, we performed a text mining approach using the Genomatix BiblioSphere. We identified signalling pathways of G-protein coupled receptors, JAK/STAT, and Integrin which contain a number of CoQ10 sensitive genes. Further analysis suggested that IL5, thrombin, vitronectin, vitronectin receptor, and C-reactive protein are regulated by CoQ10 via the transcription factor NFkappaB1. To test this hypothesis, we studied the effect of CoQ10 on the NFkappaB1-dependent pro-inflammatory cytokine TNF-alpha. As a model, we utilized the murine macrophage cell lines RAW264.7 transfected with human apolipoprotein E3 (apoE3, control) or pro-inflammatory apoE4. In the presence of 2.5 microM or 75 microM CoQ10 the LPS-induced TNF-alpha response was significantly reduced to 73.3 +/- 2.8% and 74.7 +/- 8.9% in apoE3 or apoE4 cells, respectively. Therefore, the in silico analysis as well as the cell culture experiments suggested that CoQ10 exerts anti-inflammatory properties via NFkappaB1-dependent gene expression.
Schmelzer
Constance
C
Institute of Human Nutrition and Food Science, Molecular Nutrition, Christian-Albrechts-University of Kiel, Germany.
Lindner
Inka
I
Rimbach
Gerald
G
Niklowitz
Petra
P
Menke
Thomas
T
Döring
Frank
F
D000818:Animals; D002460:Cell Line; D003198:Computer Simulation; D015870:Gene Expression / Q000187:drug effects*; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000502:physiology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; C024989:coenzyme Q10