Affiliations: Institute of Human Nutrition and Food Science,
Molecular Nutrition, Christian-Albrechts-University of Kiel, Germany | Institute of Human Nutrition and Food Science, Food
Science, Christian-Albrechts-University of Kiel, Germany | Vestische Kinder- und Jugendklinik Datteln, University
of Witten/Herdecke, Germany
Note: [] Address for correspondence: Frank Döring, Institute of Human
Nutrition and Food Science, Molecular Nutrition, Christian-Albrechts-University
of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany. Tel.: +49 431 880 3387;
Fax: +49 431 880 5658; E-mail: [email protected]
Abstract: Clinical studies demonstrated the efficacy of Coenzyme Q_{10}
(CoQ_{10}) as an adjuvant therapeutic in cardiovascular diseases,
mitochondrial myopathies and neurodegenerative diseases. More recently,
expression profiling revealed that Coenzyme Q_{10} (CoQ_{10}) 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 CoQ_{10} sensitive genes.
Further analysis suggested that IL5, thrombin, vitronectin, vitronectin
receptor, and C-reactive protein are regulated by CoQ_{10} via the
transcription factor NFκB1. To test this hypothesis, we studied the
effect of CoQ_{10} on the NF$\kappa$B1-dependent pro-inflammatory cytokine
TNF-α. 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 μM or 75 μM CoQ_{10} the LPS-induced
TNF-α 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 CoQ_{10}
exerts anti-inflammatory properties via NFκB1-dependent gene
expression.
