부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]