Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms

Sung-Yun Cho; Hee-jin Jun; Ji Hae Lee; Yaoyao Jia; Kyoung Heon Kim; Sung-Joon Lee

doi:10.1016/j.febslet.2011.09.012

Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms

FEBS Lett. 2011 Oct 20;585(20):3289-96. doi: 10.1016/j.febslet.2011.09.012. Epub 2011 Sep 17.

Authors

Sung-Yun Cho¹, Hee-jin Jun, Ji Hae Lee, Yaoyao Jia, Kyoung Heon Kim, Sung-Joon Lee

Affiliation

¹ Department of Biotechnology, The Graduate School of Biotechnology, Korea University, Seoul, Republic of Korea.

PMID: 21944868
DOI: 10.1016/j.febslet.2011.09.012

Abstract

We investigated hypocholesterolemic mechanisms of linalool, an aromatic anti-oxidative monoterpene, which is abundant in teas and essential oils. Oral administration of linalool to mice for 6 weeks significantly lowered total and low-density lipoprotein cholesterol concentrations, and HMG-CoA reductase protein expression (-46%; P<0.05) by both transcriptional and posttranscriptional mechanisms. Linalool suppressed the gene expression of HMG-CoA reductase by reducing the binding of SREBP-2 to its promoter, as assessed by qPCR and chromatin immunoprecipitation, and by inducing ubiquitin-dependent proteolysis of the HMG-CoA reductase. These findings suggest that food molecules with a pleasant scent could exert beneficial metabolic effects through multiple mechanisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acyclic Monoterpenes
Animals
Anticholesteremic Agents / pharmacology*
Cholesterol / blood
Gene Expression Regulation, Enzymologic / drug effects*
Gene Expression Regulation, Enzymologic / genetics
Hep G2 Cells
Humans
Hydroxymethylglutaryl CoA Reductases / biosynthesis*
Hydroxymethylglutaryl CoA Reductases / genetics
Insecticides / pharmacology
Lipoproteins, LDL / blood
Male
Mice
Monoterpenes / pharmacology*
Proteolysis / drug effects
Response Elements
Sterol Regulatory Element Binding Protein 2 / genetics
Sterol Regulatory Element Binding Protein 2 / metabolism*
Ubiquitin / genetics
Ubiquitin / metabolism*

Substances

Acyclic Monoterpenes
Anticholesteremic Agents
Insecticides
Lipoproteins, LDL
Monoterpenes
SREBF2 protein, human
Srebf2 protein, mouse
Sterol Regulatory Element Binding Protein 2
Ubiquitin
Cholesterol
linalool
Hydroxymethylglutaryl CoA Reductases