The Reduced Form of Coenzyme Q10 Mediates Distinct Effects on Cholesterol Metabolism at the Transcriptional and Metabolite Level in SAMP1 Mice
The Reduced Form of Coenzyme Q10 Mediates Distinct Effects on Cholesterol Metabolism at the Transcriptional and Metabolite Level in SAMP1 Mice
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DOI：
10.1002/iub.388
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发表时间：
2010-11-01
期刊：
影响因子：
4.6
通讯作者：
Doering, Frank
中科院分区：
文献类型：
--
作者：
Schmelzer, Constance;Okun, Juergen G.;Doering, Frank
对人类和小鼠的研究表明辅酶 Q(10) (CoQ(10)) 在基因表达中发挥作用。为了分析与代谢相关的这一功能，SAMP1 小鼠补充了还原（泛醇）或氧化（泛醌）形式的 CoQ(10)（500 mg/kg BW/d），持续 14 个月。 SAMP1 小鼠肝组织中的微阵列分析鉴定出 946 个基因在泛醇治疗组和对照动物之间存在差异表达（> = 1.5 倍，P < 0.05）。文本挖掘分析揭示了部分泛醇调节基因与 PPAR α 和 LXR/RXR 信号通路的功能联系。由于这些途径涉及胆固醇稳态，因此通过气相色谱/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 小鼠肝脏中去氨甾醇显着增加（2.0 倍，P < 0.001）。与此一致的是，胆固醇浓度也明显增加（1.3 倍，P < 0.057）。 Q(10)H(2) 诱导的 PPAR α 和 LXR/RXR 基因表达特征以及对胆固醇代谢的影响对于氧化形式的 CoQ(10) 并不明显。总之，CoQ(10) 的还原形式在 SAMP1 小鼠的转录和代谢水平上介导对胆固醇代谢的明显影响。 (C) 2010 IUBMB IUBMB 生活，62(11)：812-818，2010
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 PPAR alpha 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 PPAR alpha 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. (C) 2010 IUBMB IUBMB Life, 62(11): 812-818, 2010