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Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis

Bentinger, Magnus and Kania, Magdalena and Danikiewicz, Witold and Kaczorowska, Ewa and Wójcik, Jacek and Brismar, Kerstin and Dallner, Gustav and Chojnacki, Tadeusz and Swiezewska, Ewa and Tekle, Michael (2014) Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids , 1841 (7). pp. 977-986. ISSN 10-1016

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Official URL: http://www.sciencedirect.com/science/article/pii/S...


2,3-Oxidosqualene is an intermediate in cholesterol biosynthesis and 2,3:22,23-dioxidosqualene act as the substrate for an alternative pathway that produces 24(S),25-epoxycholesterol which effects cholesterol homeostasis.In light of our previous findings concerning the biological effects of certain epoxidated all-transpolyisoprenes,the effects of squalene carrying epoxy moieties on the second and third isoprene residues were investigated here. In cultures ofHepG2 cells bothmonoepoxides of squalene and one of their hydrolytic products inhibited cholesterol synthesis and stimulated the synthesis of coenzyme Q (CoQ). Upon prolonged treatment the cholesterol content of these cells and its labeling with [3H]mevalonate were reduced, while the amount and labeling of CoQ increased. Injection of the squalene monoepoxides into mice once daily for 6 days elevated the level of CoQ in their blood, but did not change the cholesterol level. The same effects were observed upon treatment of apoE-deficient mice and diabetic GK-rats. This treatment increased the hepatic level of CoQ10 in mice, but the amount of CoQ9, which is the major form, was unaffected. The presence of the active compounds in the blood was supported by the finding that cholesterol synthesis in the white blood cells was inhibited. Since the ratio of CoQ9/CoQ10 varies depending on the experimental conditions, the cells were titrated with substrate and inhibitors, leading to the conclusion that the intracellular isopentenyl-PP pool is a regulator of this ratio. Our present findings indicate that oxidosqualenes may be useful for stimulating both the synthesis and level of CoQ both in vitro and in vivo.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Lipid Biochemistry
ID Code:743
Deposited By: Ewa Swiezewska
Deposited On:18 Dec 2014 10:51
Last Modified:18 Dec 2014 10:51

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