REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE GENE-EXPRESSION BY STEROLS AND NONSTEROLS IN RAT-LIVER
REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE GENE-EXPRESSION BY STEROLS AND NONSTEROLS IN RAT-LIVER
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DOI：
10.1006/abbi.1994.1059
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发表时间：
1994-02-01
影响因子：
3.9
通讯作者：
ZHAO, ZH
中科院分区：
文献类型：
--
作者：
NESS, GC;EALES, S;ZHAO, ZH
通过测量大鼠的mRNA、蛋白质和酶活性，研究了胆固醇和非固醇调节肝脏3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶基因表达的机制，这些大鼠喂食胆固醇或给予消耗内源性固醇和非固醇或选择性消耗固醇的药物。结果发现，虽然饮食胆固醇对HMG-CoA还原酶mRNA水平的影响很小，免疫反应性蛋白质减少到几乎检测不到的水平，因为是酶活性。因此排除了对催化效率的任何可能影响。当大鼠喂食含有洛伐他汀（一种强效HMG-CoA还原酶抑制剂，可阻断非固醇和固醇的合成）的饲料时，观察到HMG-CoA还原酶mRNA和活性均增加了15- 20倍。然而，HMG-CoA还原酶免疫反应性蛋白增加超过200倍。当内源性甾醇被选择性地耗尽，通过抑制角鲨烯合成酶与扎戈齐酸A，还原酶mRNA中观察到的增加是类似的免疫反应蛋白质和酶活性。这与内源性固醇在转录水平发挥作用而内源性非固醇在翻译水平发挥作用的概念一致。结果表明，在整个动物中，甾醇可能在mRNA水平上发挥作用，而非甾醇在HMG-CoA还原酶蛋白水平上发挥其调节作用。(C)1994年出版社出版。
The mechanisms by which sterols and nonsterols regulate hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene expression was investigated by measuring mRNA, protein, and enzyme activity in rats fed cholesterol or given drugs that deplete both endogenous sterols and nonsterols or that selectively deplete sterols. It was found that while dietary cholesterol had little effect on HMG-CoA reductase mRNA levels; immunoreactive protein was reduced to barely detectable levels, as was enzyme activity. Any possible effect on catalytic efficiency is thus ruled out. When rats were fed diets containing Lovastatin, a potent HMG-CoA reductase inhibitor which blocks synthesis of both nonsterols and sterols, similar 15- to 20-fold increases were observed for both HMG-CoA reductase mRNA and activity. However, HMG-CoA reductase immunoreactive protein was increased more than 200-fold. When endogenous sterols were selectively depleted by inhibiting squalene synthase with Zargozic acid A, the increase observed in reductase mRNA was similar to that seen in immunoreactive protein and enzyme activity. This is consistent with the concept that endogenous sterols exert their effects at the level of transcription while endogenous nonsterols act at the level of translation. The results suggest that in whole animals, sterols likely act at the level of mRNA while nonsterols exert their regulatory effects at the level of HMG-CoA reductase protein. (C) 1994 Academic Press, Inc.