Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Kiel, Germany.
IUBMB Life. 2010 Nov;62(11):812-8. doi: 10.1002/iub.388.
Studies in humans and mice indicate a role for coenzyme Q(10) (CoQ(10)) in gene expression. To analyze this function in relation to metabolism, SAMP1 mice were supplemented with the reduced (ubiquinol) or oxidized (ubiquinone) form of CoQ(10) (500 mg/kg BW/d) for 14 months. Microarray analyses in liver tissues of SAMP1 mice identified 946 genes as differentially expressed between ubiquinol-treated and control animals (≥1.5-fold, P < 0.05). Text mining analyses revealed for a part of the ubiquinol-regulated genes, a functional connection in PPARα and LXR/RXR signalling pathways. Because these pathways are involved in cholesterol homeostasis, relevant metabolites were determined by gas chromatography/mass spectrometry (GC/MS). We found a significant increase of desmosterol (2.0-fold, P < 0.001) in the liver of ubiquinol-supplemented SAMP1 mice when related to control animals. In agreement, cholesterol concentrations were also distinctly increased (1.3-fold, P = 0.057). The Q(10)H(2)-induced PPARα and LXR/RXR gene expression signatures and effects on cholesterol metabolism were not apparent for the oxidized form of CoQ(10). In conclusion, the reduced form of CoQ(10) mediates distinct effects on cholesterol metabolism at the transcriptional and metabolite level in SAMP1 mice.
在人类和小鼠中的研究表明辅酶 Q(10)(CoQ(10))在基因表达中起作用。为了分析这种与代谢相关的功能，用还原形式（泛醇）或氧化形式（泛醌）的 CoQ(10)(500mg/kgBW/d)对 SAMP1 小鼠补充 14 个月。SAMP1 小鼠肝组织的微阵列分析确定了 946 个基因在泛醇处理和对照动物之间差异表达（≥1.5 倍，P<0.05）。文本挖掘分析揭示了一部分泛醇调节的基因，在 PPARα 和 LXR/RXR 信号通路中有功能连接。由于这些途径参与胆固醇稳态，通过气相色谱/质谱（GC/MS）测定相关代谢物。我们发现，与对照动物相比，补充泛醇的 SAMP1 小鼠肝脏中的去甲胆固醇（desmosterol）显著增加（2.0 倍，P<0.001）。与此一致，胆固醇浓度也明显增加（1.3 倍，P=0.057）。氧化形式的 CoQ(10) 对 PPARα 和 LXR/RXR 基因表达特征和胆固醇代谢没有明显影响。总之，还原形式的 CoQ(10)在 SAMP1 小鼠中在转录和代谢物水平上对胆固醇代谢具有明显的影响。
