HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hidaka, Y. Articles by Kamei, T. Search for Related Content PubMed PubMed Citation Articles by Hidaka, Y. Articles by Kamei, T. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 31, 2087-2094, Copyright © 1990 by Lipid Research, Inc.

ARTICLES

Regulation of squalene epoxidase in HepG2 cells

Y Hidaka, T Satoh and T Kamei
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.

Regulation of squalene epoxidase in the cholesterol biosynthetic pathway was studied in a human hepatoma cell line, HepG2 cells. Since the squalene epoxidase activity in cell homogenates was found to be stimulated by the addition of Triton X-100, enzyme activity was determined in the presence of this detergent. Incubation of HepG2 cells for 18 h with L-654,969, a potent competitive inhibitor of 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase, increased squalene epoxidase activity dose-dependently. On the other hand, low density lipoprotein (LDL) and 25-hydroxy-cholesterol decreased the enzyme activity. These results demonstrate that squalene epoxidase is regulated by the concentrations of endogenous and exogenous sterols. The affinity of the enzyme for squalene was not changed by treatment with L-654,969. Cytosolic (S105) fractions, prepared from HepG2 cells treated with or without L-654,969, had no effect on microsomal squalene epoxidase activity of HepG2 cells, in contrast to the stimulating effect of S105 fractions from rat liver homogenate. Mevalonate, LDL, and oxysterol treatment abolished the effect of L-654,969. Simultaneous addition of cycloheximide and actinomycin D also prevented enzyme induction in HepG2 cells. From these results, the change in squalene epoxidase activity is thought to be caused by the change in the amount of enzyme protein. It is further suggested that squalene epoxidase activity is suppressed only by sterols, not by nonsterol derivative(s) of mevalonate, in contrast to the regulation of HMG-CoA reductase.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Gupta and T. D. Porter Garlic and Garlic-Derived Compounds Inhibit Human Squalene Monooxygenase J. Nutr., June 1, 2001; 131(6): 1662 - 1667. [Abstract] [Full Text]

				Y. Nakamura, J. Sakakibara, T. Izumi, A. Shibata, and T. Ono Transcriptional Regulation of Squalene Epoxidase by Sterols and Inhibitors in HeLa Cells J. Biol. Chem., April 5, 1996; 271(14): 8053 - 8056. [Abstract] [Full Text] [PDF]

				J. Sakakibara, R. Watanabe, Y. Kanai, and T. Ono Molecular Cloning and Expression of Rat Squalene Epoxidase J. Biol. Chem., January 6, 1995; 270(1): 17 - 20. [Abstract] [Full Text] [PDF]