Change search
ReferencesLink to record
Permanent link

Direct link
Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet.
Show others and affiliations
2014 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1388-1918, Vol. 1841, no 7, 977-986 p.Article in journal (Refereed) Published
Abstract [en]

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-trans-polyisoprenes, the effects of squalene carrying epoxy moieties on the second and third isoprene residues were investigated here. In cultures of HepG2 cells both monoepoxides 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 [H-3]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.

Place, publisher, year, edition, pages
2014. Vol. 1841, no 7, 977-986 p.
Keyword [en]
Mevalonate pathway, Squalene epoxides, Coenzyme Q induction, Cholesterol inhibition, Dolichol
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-105884DOI: 10.1016/j.bbalip.2014.03.007ISI: 000336698800007OAI: diva2:733418
Swedish Research Council, K2014-55X-22514-01-3


Available from: 2014-07-09 Created: 2014-07-08 Last updated: 2014-07-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Bentinger, MagnusDallner, GustavTekle, Michael
By organisation
Department of Biochemistry and Biophysics
In the same journal
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 40 hits
ReferencesLink to record
Permanent link

Direct link