Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms.
نویسندگان
چکیده
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.
منابع مشابه
Matrix metalloproteinase-2 mediates a mechanism of metabolic cardioprotection consisting of negative regulation of the sterol regulatory element-binding protein-2/3-hydroxy-3-methylglutaryl-CoA reductase pathway in the heart.
Previously, we reported that cardiac matrix metalloproteinase (MMP)-2 is upregulated in hypertensive mice. How MMP-2 affects the development of cardiac disease is unclear. Here, we report that MMP-2 protects from hypertensive cardiac disease. In mice infused with angiotensin II, the lack of MMP-2 (Mmp2(-/-)) did not affect the severity of the hypertension but caused cardiac hypertrophy to devel...
متن کاملGene expression of sterol regulatory element-binding proteins in hamster small intestine.
Gene expression of sterol regulatory element-binding proteins 1a, 1c, and 2 (SREBP-1a, -1c, and -2) and of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and the low density lipoprotein (LDL) receptor was examined in hamster small intestine. SREBP-1c transcript predominated over SREBP-1a. mRNA levels for SREBP-1a, -1c, and -2, LDL receptor, and HMG-CoA synthase wer...
متن کاملUbiquitination of 3-hydroxy-3-methylglutaryl-CoA reductase in permeabilized cells mediated by cytosolic E1 and a putative membrane-bound ubiquitin ligase.
The endoplasmic reticulum (ER) enzyme, 3-hydroxy-3-methylglutaryl-CoA reductase, catalyzes the production of mevalonate, a rate-controlling step in cholesterol biosynthesis. Excess sterols promote ubiquitination and subsequent degradation of reductase as part of a negative feedback regulatory mechanism. To characterize the process in more detail, we here report the development of a permeabilize...
متن کاملAncient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet–associated endoplasmic reticulum membranes
Sterol-induced binding to Insigs in endoplasmic reticulum (ER) membranes triggers ubiquitination of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase. This ubiquitination, which is mediated by Insig-associated ubiquitin ligases gp78 and Trc8, is obligatory for extraction of reductase from lipid droplet-associated ER membranes into the cytosol for proteasome-mediated, ...
متن کاملNF-Y has a novel role in sterol-dependent transcription of two cholesterogenic genes.
The transcription of farnesyl diphosphate (FPP) synthase is regulated up to 30-fold by the sterol status of the cell. Point mutations in a 6-base pair ATTGGC sequence in the promoter disrupt both sterol-dependent transcription in vivo as well as binding of the transcription factor NF-Y in vitro. Co-transfection of cells with NF-YA29, a dominant negative form of NF-Y, and various promoter-report...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- FEBS letters
دوره 585 20 شماره
صفحات -
تاریخ انتشار 2011