Abstract：
:Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researchers are currently investigating the use of PFTIs for the treatment of eukaryotic pathogens. This "piggy-back" approach not only accelerates the development of a chemotherapeutic agent for protozoan pathogens but is also a means of mitigating the costs associated with de novo drug design. PFTIs have already been shown to be efficacious in the treatment of eukaryotic pathogens in animal models, including both Trypanosoma brucei, the causative agent of African sleeping sickness, and Plasmodium falciparum, one of the causative agents of malaria. Here, current evidence and progress are summarized that support the targeting of protein farnesyltransferase for the treatment of parasitic diseases.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Eastman RT,Buckner FS,Yokoyama K,Gelb MH,Van Voorhis WCdoi
10.1194/jlr.R500016-JLR200keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
233-40issue
2eissn
0022-2275issn
1539-7262pii
R500016-JLR200journal_volume
47pub_type
杂志文章,评审abstract：:Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate. Insulin-resistant, hypertri...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P068585
更新日期：2016-11-01 00:00:00
abstract：:The novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor CP-113,818 has been characterized in vitro against ACAT isolated from liver and intestine from a variety of species including human subjects, and in vivo in cholesterol-fed rats, hamsters, rabbits, and two species of nonhuman primates. CP-113,818 is a pot...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Studies on plasma triglycerides (TG) were performed in 10 nonobese and 16 obese patients with hypothyroidism and in 13 with hyperthyroidism. Nonobese, hypothyroid patients generally had normal levels of TG, but obese patients often had hypertriglyceridemia. In most hypothyroid patients 1-thyroxine treatment lowered pl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:Sequence homology indicates the existence of three human cytosolic acyl protein thioesterases, including APT1 that is known to depalmitoylate H- and N-Ras. One of them is the lysophospholipase-like 1 (LYPLAL1) protein that on the one hand is predicted to be closely related to APT1 but on the other hand might also func...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M019851
更新日期：2012-01-01 00:00:00
abstract：:The formation of cholic acid from 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA) was studied in two normal subjects. [3H]THCA and [14C]cholic acid were administered intravenously by simultaneous injection and the specific activities (percent injected amount/mumol) of [3H]- and [14C]cholic acid w...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1977-09-01 00:00:00
abstract：:Three colipases were purified from pancreas of two birds (ostrich and turkey) and one mammal (dromedary). After acidic and/or heat treatment and precipitation by sulfate ammonium and then ethanol, cofactors were purified by Sephadex G-50 gel filtration followed by ion-exchange chromatography first on Mono S and then o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600242-JLR200
更新日期：2006-12-01 00:00:00
abstract：:The relationship between the cholesterol 7 alpha-hydroxylase activity and the pool of free cholesterol in rat liver microsomes was studied under experimental conditions aimed to stimulate (biliary drainage, cholestyramine treatment, and lymphatic drainage) as well as inhibit (chenodeoxycholic acid treatment) bile acid...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly exp...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800666-JLR200
更新日期：2009-06-01 00:00:00
abstract：:We investigated the formation and pharmacology of prostaglandin E(3) (PGE(3)) derived from fish oil eicosapentaenoic acid (EPA) in human lung cancer A549 cells. Exposure of A549 cells to EPA resulted in the rapid formation and export of PGE(3.) The extracellular ratio of PGE(3) to PGE(2) increased from 0.08 in control...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M300455-JLR200
更新日期：2004-06-01 00:00:00
abstract：:The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who h...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P023994
更新日期：2012-05-01 00:00:00
abstract：:Mice with a targeted mutation of 3beta-hydroxysterol Delta(7)-reductase (Dhcr7) that cannot convert 7-dehydrocholesterol to cholesterol were used to identify the origin of fetal sterols. Because their heterozygous mothers synthesize cholesterol normally, virtually all sterols found in a Dhcr7 knockout fetus having a D...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600141-JLR200
更新日期：2006-07-01 00:00:00
abstract：:Apolipoprotein C-II (apoC-II) plays a critical role in the metabolism of plasma lipoproteins as an activator for lipoprotein lipase. Human apoC-II consists of 79 amino acid residues (pro-apoC-II). A minor fraction is converted to a mature form by cleavage at the site QQDE releasing the 6 amino-terminal residues. We ha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:This study describes a variant of familial apoA-I deficiency associated with a moderate risk for premature coronary artery disease. The proband, a 25-year-old man of Philippine origin, and his 62-year-old maternal aunt had peripheral corneal opacification, xanthelasma, and planar xanthoma; the aunt had coronary artery...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:An elevated plasma concentration of lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. Life style modification and currently available drugs either fail to effectively lower plasma Lp(a) levels or do not result in clinical benefit. However, lipoprotein apheresis is very efficient in decr...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R056549
更新日期：2016-10-01 00:00:00
abstract：:The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previousl...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M034124
更新日期：2013-04-01 00:00:00
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,...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M011817
更新日期：2011-05-01 00:00:00
abstract：:A molecular model was built for human lecithin:cholesterol acyltransferase (LCAT) based upon the structural homology between this enzyme and lipases (Peelman et al. 1998. Prot. Sci. 7: 585-597). We proposed that LCAT belongs to the alpha/beta hydrolase fold family, and that the central domain of LCAT consists of a mix...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy....
journal_title：Journal of lipid research
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1194/jlr.P800042-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies agai...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:The activity of phospholipase A on phosphatidyl choline and phosphatidal choline spread as monolayers on phosphate buffers containing snake venom (Crotalus atrox or Naja naja) was studied by measuring the fall of surface potential as a function of time, pH, film pressure, temperature, and concentrations of phosphate a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1966-03-01 00:00:00
abstract：:The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has been learned about ceramide generation by activation of sphingomyelinases in response to IL-1, the contribution o...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M065920
更新日期：2016-08-01 00:00:00
abstract：:Male Sprague-Dawley rats were fed diets that contained 20% by weight soybean oil or rapeseed oil (21% and 43% erucic acid) for 7 days. The rapeseed oil diets increased the cardiac triacylglycerol content 5-fold and 25-fold, respectively, above control values. Hearts were removed from the animals and perfused with modi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The simultaneous exchange of (3h)tocopherol and (14C)cholesterol between rat plasma, rat plasma lipoproteins, and RBC was studied in vitro to compare quantitavely (a) the fractional exchange rates and (b) the half-times for isotope equilibration. In all incubations of RBC with plasma or with plasma lipoprotein fractio...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1975-01-01 00:00:00
abstract：:In an approach to the identification of proteins involved in the side chain degradation of bile salt biosynthesis, the photolabile 7,7-azo derivatives of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
abstract：:Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:Hyperlipoproteinemia contributes both to kidney disease progression and the development of atherosclerosis. Elevated high density lipoprotein cholesterol and apolipoprotein A-I (apoA-I) serum levels are independent factors protective against the atherosclerotic process. We examined the effects in a transgenic rat mode...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-07-01 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：:Two novel mutations of the low density lipoprotein (LDL)-receptor gene were found in two Italian familial hypercholesterolemia (FH)-heterozygotes. The first mutation was an 18 nucleotide duplication in exon 8 which is preceded by an A-->T transversion. The translation product of the mutant allele was predicted to be a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Recent reports from this laboratory indicate that exposure of cholesterol-loaded macrophages to high density lipoprotein 3 (HDL3) stimulates not only cholesterol efflux, but also results in a two- to threefold increase in apoE accumulation in the media (Dory, L., 1989. J. Lipid Res. 30: 809-816). The present experimen...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Previously, our laboratory demonstrated that ceramide-1-phosphate (C1P) specifically activated group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) in vitro. In this study, we investigated the chain length specificity of this interaction. C1P with an acyl-chain of >or=6 carbons efficiently activated cPLA(2)alpha in v...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800367-JLR200
更新日期：2009-10-01 00:00:00
