Influence of peroxisome proliferator-activated receptor α on ubiquinone biosynthesis
Influence of peroxisome proliferator-activated receptor α on ubiquinone biosynthesis
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过氧化物酶体增殖物激活受体α对泛醌生物合成的影响
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
G. Dallner
中科院分区：
文献类型：
--
作者：
M. Turunen;J. Peters;F. Gonzalez;S. Schedin;G. Dallner
利用过氧化物酶体增殖物激活受体α（PPARα）基因敲除小鼠研究了过氧化物酶体增殖物对泛醌生物合成的调控。向对照小鼠施用2-（二乙基己基）邻苯二甲酸酯导致肝脏中泛醌水平升高，而长萜醇、长萜-P和胆固醇浓度保持不变。在PPARα缺失小鼠中，这些脂质的水平与对照水平相似，给予过氧化物酶体增殖剂不会增加泛醌的水平。泛醌水平的增加是合成增加的结果。肝脏、肾脏和心脏中的诱导作用最明显，这些器官中的PPARα水平相对较高。当过氧化氢的组织浓度升高，抑制过氧化氢酶活性与氨基三唑，泛醌的量没有增加，这表明泛醌合成的诱导发生通过一个直接的机制。过氧化物酶体增殖剂处理后，对照组中的分支点酶FPP合酶、角鲨烯合酶、顺式异戊二烯基转移酶、反式异戊二烯基转移酶和NPHB转移酶的活性显著增加，但未在PPARα缺失小鼠中增加。这些数据表明，给予过氧化物酶体增殖剂后，泛醌生物合成的诱导依赖于通过调节某些甲羟戊酸途径酶的PPARα。
The control of ubiquinone biosynthesis by peroxisome proliferators was investigated using peroxisome proliferator activated receptor α (PPARα)-null mice. Administration of 2-(diethylhexyl)phthalate to control mice resulted in elevated ubiquinone levels in the liver, while dolichol, dolichyl-P and cholesterol concentrations remained unchanged. In PPARα-null mice, the level of these lipids were similar to control levels and administration of the peroxisome proliferator did not increase the levels of ubiquinone. The increase in ubiquinone levels was the result of increased synthesis. Induction was most pronounced in liver, kidney and heart, which have relatively high levels of PPARα. When the tissue concentration of hydrogen peroxide was elevated by inhibition of catalase activity with aminotriazole, the amount of ubiquinone was not increased, suggesting that the induction of ubiquinone synthesis occured through a direct mechanism. The activities of branch-point enzymes FPP-synthase, squalene synthase, cis-prenyltransferase, trans-prenyltransferase and NPHB-transferase were substantially increased in control but not in PPARα-null mice after treatment with peroxisome proliferators. These data suggest that the induction of ubiquinone biosynthesis after administration of peroxisome proliferators is dependent on the PPARα through regulation of some of the mevalonate pathway enzymes.
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DOI：
--
发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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作者：
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