Abstract：
:Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is the rate-controlling enzyme of cholesterol synthesis, and owing to its biological and pharmacological relevance, researchers have investigated several compounds capable of modulating its activity with the hope of developing new hypocholesterolemic drugs. In particular, polyphenol-rich extracts were extensively tested for their cholesterol-lowering effect as alternatives, or adjuvants, to the conventional statin therapies, but a full understanding of the mechanism of their action has yet to be reached. Our work reports on a detailed kinetic and equilibrium study on the modulation of HMGR by the most-abundant catechin in green tea, epigallocatechin-3-gallate (EGCG). Using a concerted approach involving spectrophotometric, optical biosensor, and chromatographic analyses, molecular docking, and site-directed mutagenesis on the cofactor site of HMGR, we have demonstrated that EGCG potently inhibits the in vitro activity of HMGR (K(i) in the nanomolar range) by competitively binding to the cofactor site of the reductase. Finally, we evaluated the effect of combined EGCG-statin administration.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Cuccioloni M,Mozzicafreddo M,Spina M,Tran CN,Falconi M,Eleuteri AM,Angeletti Mdoi
10.1194/jlr.M011817subject
Has Abstractpub_date
2011-05-01 00:00:00pages
897-907issue
5eissn
0022-2275issn
1539-7262pii
jlr.M011817journal_volume
52pub_type
杂志文章abstract：:We have studied the recognition and uptake of acid lipase by human fibroblasts in order to determine requirements for localization and function of the enzyme in lysosomes. Our approach was based on evidence that a number of acid hydrolases involved in mucopolysaccharide metabolism are secreted from cultured fibroblast...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-01-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) is a receptor-active lipid mediator with a broad range of biological effects. Ovarian cancer cells synthesize LPA, which promotes their motility, growth, and survival. We show that a murine homolog of a human protein previously reported to hydrolyze LPA is a highly selective detergent-stimu...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300188-JLR200
更新日期：2003-10-01 00:00:00
abstract：:The early premalignant liver provides a model in which to study metabolic alterations that may be permissive for the development of full malignancy. Although there are biochemical changes in this model, there are no detectable morphological ones when compared with a normal, fully differentiated liver. The maintenance ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Mutations in the genes coding for patatin-like phospholipase domain-containing 1 (PNPLA1) and α/β-hydrolase domain-containing 5 (ABHD5), also known as comparative gene identification 58, are causative for ichthyosis, a severe skin barrier disorder. Individuals with mutations in either of these genes show a defect in e...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089771
更新日期：2018-12-01 00:00:00
abstract：:Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, sa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M200405-JLR200
更新日期：2003-04-01 00:00:00
abstract：:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximate...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800089-JLR200
更新日期：2009-04-01 00:00:00
abstract：:The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by nor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:The effects of vitamin E on the activity of membrane-dependent enzymes suggest that it acts indirectly by modifying some properties of the lipid host. The effects of alpha-tocopherol (alpha-T) and alpha-tocopherol hemisuccinate (alpha-THS) on phospholipid monolayer structure, curvature, and bending elasticity were exa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300146-JLR200
更新日期：2003-10-01 00:00:00
abstract：:In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate specie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019927
更新日期：2012-01-01 00:00:00
abstract：:Apolipoprotein A-V (apoA-V) first gained attention as a regulator of triglycerides through transgenic mouse studies. Furthermore, peroxisome proliferator-activated receptor alpha (PPARalpha) agonists such as fenofibrate increase apoA-V mRNA expression. Our group recently developed the first assay to quantitate serum a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.C500010-JLR200
更新日期：2005-08-01 00:00:00
abstract：:In specialized cell types, lysosome-related organelles support regulated secretory pathways, whereas in nonspecialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089979
更新日期：2019-04-01 00:00:00
abstract：:The composition of the emulsified oil and of the micellar phases obtained when a glyceride-fatty acid mixture is dispersed in bile salt solution has been defined. The micellar phase in equilibrium with the emulsified oil phase was obtained by filtration through Millipore filters. The behavior of different lipids in su...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1967-11-01 00:00:00
abstract：:A method for quantitative analysis of serum bile acids by capillary gas--liquid chromatography--mass spectrometry is described. The main features of this method are a Grob-type barium carbonate/polyethyleneglycol 20,000 glass capillary column, an all-glass capillary interface, use of the lipophilic anion exchanger DEA...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
abstract：:Vitamin E is a naturally occurring fat-soluble antioxidant which has been proposed as a treatment for both primary and secondary protection against cardiovascular (CV) events. Promising data from observational epidemiological studies associating higher vitamin E dietary intake with lower risk of CV events have not bee...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R026641
更新日期：2013-09-01 00:00:00
abstract：:Oxidized forms of cholesterol (oxysterols) are present in atherosclerotic lesions and may play an active role in lesion development. For example, 7-ketocholesterol (7KC) inhibits cholesterol efflux from macrophage foam cells induced by apolipoprotein A-I (apoA-I). Such oxysterols may promote foam cell formation in ath...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:After crossing floxed stearoyl-CoA desaturase-1 (Scd1fl/fl) mice with LDL receptor-null (ldlr-/-) mice, and then Villin Cre (VilCre) mice, enterocyte Scd1 expression in Scd1fl/fl/ldlr-/-/VilCre mice was reduced 70%. On Western diet (WD), Scd1fl/fl/ldlr-/- mice gained more weight than Scd1fl/fl/ldlr-/-/VilCre mice (P <...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M083527
更新日期：2018-10-01 00:00:00
abstract：:Ceramidases catalyze the cleavage of ceramides into sphingosine and fatty acids. Previously, we reported on the use of the RBM14 fluorogenic ceramide analogs to determine acidic ceramidase activity. In this work, we investigated the activity of other amidohydrolases on RBM14 compounds. Both bacterial and human purifie...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D061564
更新日期：2015-10-01 00:00:00
abstract：:Recent studies from our laboratory (Yancey, P.G., and R. W. St. Clair. 1992. Arterioscler. Thromb. 12: 1291-1304) have shown that cultured peritoneal macrophages from White Carneau (WC) pigeons clear cholesteryl esters at a slower rate than do macrophages from Show Racer (SR) pigeons (9% per 24 h vs. 42% per 24 h, res...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:This article presents a novel methodology for the analysis of ethanolamine glycerophospholipid (PE) and lysoPE molecular species directly from lipid extracts of biological samples. Through brief treatment of lipid extracts with fluorenylmethoxylcarbonyl (Fmoc) chloride, PE and lysoPE species were selectively derivatiz...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500007-JLR200
更新日期：2005-07-01 00:00:00
abstract：:Skeletal muscle has two circulatory routes, nutritive (in contact with muscle) and non-nutritive (part of which is located in the connective tissue), and the balance of flow between the two is controlled by neural input and circulating vasomodulators. The purpose of this study was to assess muscle triglyceride hydroly...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:The absorption and distribution of deuterated trans- and cis-13-octadecenoic acid (13t-18:1 and 13c-18:1) in plasma lipids were compared to deuterated cis-9-octadecenoic acid (9c-18:1) in two young adult male subjects. A mixture of triglycerides was fed in a multiple-labeled experiment where each triglyceride containe...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:Alzheimer's disease (AD) is characterized by an extensive accumulation of amyloid-β (Aβ) peptide, which triggers a set of deleterious processes, including synaptic dysfunction, inflammation, and neuronal injury, leading to neuronal loss and cognitive impairment. A large body of evidence supports that nuclear receptor ...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R075556
更新日期：2017-10-01 00:00:00
abstract：:It has been suggested that phytosterol and phytostanol esters possess similar cholesterol-lowering properties, however, whether mechanisms responsible are identical has not been addressed. To address this question, cholesterol plasma levels, absorption, biosynthesis, and turnover were measured in 15 hypercholesterolem...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-05-01 00:00:00
abstract：:Previously, we identified the low density lipoprotein receptor (LDLR) promoter region -17 to -1 as a novel sterol-independent regulatory element (SIRE) that mediates the stimulating effect of oncostatin M (OM). The goal of this study was to identify the OM-induced transcription activator that binds to the SIRE sequenc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m200126-jlr200
更新日期：2002-09-01 00:00:00
abstract：:Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essent...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.TR119000383
更新日期：2020-05-01 00:00:00
abstract：:The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary and intestinal removal of neutral sterols. Here, we identify a binding site for the orphan nuclear receptor liver receptor homolog-1 (LRH-1) at nt 134-142 of the ABCG5/ABCG8 intergenic region necessary for the activity of both the ABCG...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.C400002-JLR200
更新日期：2004-07-01 00:00:00
abstract：:Quantitative aspects of the binding of free fatty acid to human erythrocytes were studied by measuring the distribution of various amounts of [1-(14)C]lauric acid between washed human erythrocytes and defatted human plasma albumin. Incubations were done at 37 degrees C in an isotonic phosphate-buffered salt solution. ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-07-01 00:00:00
abstract：:Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was perfor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Diseases such as obesity, diabetes, and atherosclerosis result from multiple genetic and environmental factors, and importantly, interactions between genetic and environmental factors. Identifying susceptibility genes for these diseases using genetic and genomic technologies is accelerating, and the expectation over t...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R600026-JLR200
更新日期：2006-12-01 00:00:00
