... Accession Number : AD0294432. Title : CHOLESTEROL AND FATTY ACID BIOSYNTHESIS IN BRAIN. Corporate Author : ROME UNIV (ITALY). ...
DTIC Science & Technology
... Accession Number : AD0267228. Title : CHOLESTEROL AND FATTY ACID BIOSYNTHESIS IN BRAIN. Corporate Author : MILAN UNIV (ITALY). ...
Sprague-Dawley rats of both sexes were treated for three months with BM 15,766, an inhibitor of cholesterol biosynthesis in conjunction with standard or high-fat and high-cholesterol diets. In serum and livers of all drug-treated rats lowered cholesterol concentration associated with an increase of ...
PubMed
The Smith-Lemli-Opitz syndrome (SLOS) is the first-described in a growing family of hereditary defects in cholesterol biosynthesis, and presents with a spectrum of serious abnormalities, including multiple dysmorphologies, failure to thrive, cognitive and behavioral impairments, and retinopathy. Using a pharmacologically induced rat ...
PubMed Central
Biochemically, SLOS is caused by disruption of the DHCR7 gene, which is responsible for the final step in the production of cholesterol; this results in low cholesterol levels and an accumulation of toxic byproducts of cholesterol biosynthesis in the blood, nervous system, and other tissues.
Cancer.gov
The Smith�Lemli�Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation disorder caused by an inborn error of post-squalene cholesterol biosynthesis. Deficient cholesterol synthesis in SLOS is caused by inherited mutations of 3?-hydroxysterol-?7 reductase gene (DHCR7). DHCR7 deficiency impairs ...
Recent insights into the Smith-Lemli-Opitz syndrome. The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation disorder caused by an inborn error of post-squalene cholesterol biosynthesis. Deficient cholesterol synthesis in SLOS is caused by inherited mutations of ...
Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies. Patients with desmosterolosis have elevated levels of the cholesterol precursor desmosterol, in plasma, tissue, and cultured cells; this abnormality suggests a deficiency of the enzyme 3?-hydroxysterol ?24-reductase (DHCR24), which, ...
Cholesterol is highly enriched in the brain, and plays a key role in synapse formation and function. The brain does not derive cholesterol from the circulation; instead, the majority of cholesterol is made in glia and secreted in form of lipoproteins. Neurons can synthesize cholesterol, but the extent of neuronal ...
The Smith-Lemli-Opitz syndrome (SLOS) is an often lethal birth defect resulting from mutations in the gene responsible for the synthesis of the enzyme 3beta-hydroxy-steroid-Delta7-reductase, which catalyzes the reduction of the double bond at carbon 7 on 7-dehydrocholesterol (7-DHC) to form unesterified cholesterol. We hypothesize that the deficiency in ...
Smith-Lemli-Opitz/RSH syndrome (SLOS), a relatively common birth-defect mental-retardation syndrome, is caused by mutations in DHCR7, whose product catalyzes an obligate step in cholesterol biosynthesis, the conversion of 7-dehydrocholesterol to cholesterol. A null mutation in the murine Dhcr7 causes an identical biochemical defect to ...
Normally a balance of bile salts, lecithin and cholesterol keep gallstones from forming. If there are abnormally high levels of bile salts or, more commonly, cholesterol, stones can form. ...
MedlinePLUS
A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular ...
Energy Citations Database
Insig-1 and Insig-2, two closely related proteins, are essential for feedback inhibition of cholesterol biosynthesis. Here, we characterized a line of epidermal-specific, Insig-double knockout (Epi-Insig-DKO) mice lacking both Insigs in epidermis. At birth, Epi-Insig-DKO mice were indistinguishable from control littermates, but thereafter they failed to ...
Phycomyces is a fungal producer of beta-carotene and other beneficial metabolites. Several erg mutants of Phycomyces, originally selected to study the effects of membrane alteration on physiological responses, have now been used to gain information about sterol biosynthesis in filamentous fungi. One mutant, H23, and its progeny were found to be blocked at episterol C-5 ...
(C). In Dhcr7�/� animals, abnormal profiles include vesicles with condensed material surrounded secretory vesicles in animals with inborn errors of cholesterol synthesis, cholesterol cannot be substituted derived, and may account for the formation of some vesicles. Upon extraction of cholesterol and synthetic
E-print Network
... and abnormal lipid metabolism is discussed. (Author). Descriptors : *CHOLESTEROL, *FATTY ACIDS, *LIPIDS, *PROTEINS, BIOCHEMISTRY ...
... If I Had - Abnormal Cholesterol on Routine Blood Work - Dr. Lori Mosca, MD, MPh, PhD, NewYork Presbyterian ... If I Had - Abnormal Cholesterol on Routine Blood Work - Dr. Lori Mosca, MD, MPh, PhD, NewYork Presbyterian ...
Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by ...
Animal-based biotechnologies involve the use of domestic animals for the production of pharmaceuticals and various proteins in milk and eggs, as disease models, as tools for stem cell research and animal cloning, and as sources of organs for xenotransplantation into humans. Avian species offer several advantages over mammalian models, and they have been used historically to advance the fields of ...
... Descriptors : *CARDIAC GLYCOSIDES, *ELECTROLYTES(PHYSIOLOGY), *HEART, *IONS, BIOCHEMISTRY, BIOSYNTHESIS, CELLS(BIOLOGY ...
Recent evidence suggests that the major pathways mediating cell cholesterol homeostasis respond to a common signal: active membrane cholesterol. Active cholesterol is the fraction that exceeds the complexing capacity of the polar bilayer lipids. Increments in plasma membrane cholesterol exceeding this threshold ...
The distribution of cellular unesterified cholesterol was studied in fibroblasts, which had been depleted of plasma membrane sphingomyelin by exposure to exogenous sphingomyelinase. This treatment has previously been shown to induce an increase in cholesterol esterification, a decrease in the biosynthesis of ...
The RAH/Smith-Lemli-Opitz syndrome (RAH/SLOS) is an autosomal recessive malformation syndrome associated with increased levels of 7-dehydrocholesterol (7-DHC) and a defect of cholesterol biosynthesis at the level of 3{beta}-hydroxy-steroid-{Delta}{sup 7}-reductase (7-DHC reductase). Because rats exposed to inhibitors of 7-DHC reductase during development ...
Whole-body x irradiation of rats has been shown to result in an increase in the rate of cholesterol biosynthesis in liver and adrenal glands. This has been demonstrated by determination of the incorporation of slices, and by the incorporation of tritium labeled body water into cholesterol. The effect was evident 24 hours ...
After administration of polychlorinated biphenly (PCB) at 0.055 (w/w) of the diet to Wistar rats for 30 days, followed by intraperitioneal injection of tritiated water, (/sup 14/C)mevalonate, and (/sup 14/C)acetate, there was a decrease in cholesterol biosynthesis in rat liver. No significant change in cholesterol formation was ...
The free and esterified cholesterols of plasma low density lipoprotein (LDL) were extracted with heptane and replaced with 25-hydroxycholesteryl oleate. The resulting particle, designated r-[25-HC oleate]LDL, bound to LDL receptors on human fibroblasts, was taken up by adsorptive endocytosis and was hydrolyzed in lysosomes in a manner similar to that of native LDL. The ...
Incubation of fibroblasts derived from patients with type-C Niemann-Pick disease with low density lipoprotein results in excessive intracellular accumulation of unesterified cholesterol. Cytochemical techniques revealed that this abnormal cholesterol accumulation is associated not only with a massive storage of ...
Smith-Lemli-Opitz syndrome (SLOS) is a mental retardation/multiple congenital anomaly syndrome. The gene(s) involved has not been mapped or cloned, but, recently, a biochemical abnormality in cholesterol biosynthesis has been shown to occur in most SLOS patients. The defect is suspected to occur in the penultimate step of the ...
Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol ...
HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis that catalyzes the production of mevalonate. In addition to being a precursor of cholesterol, mevalonate is required by cells for DNA synthesis and cell cycle progression. We have i...
National Technical Information Service (NTIS)
Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors (PPAR), which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fib...
EPA Science Inventory
Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors, which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fibrate th...
Opposite Regulation of Cholesterol Levels by the Phosphatase and Hydrolase Domains of Soluble of sEH with cholesterol-related disorders, per- oxisome proliferator-activated receptor activity, and the isopre- noid/cholesterol biosynthesis pathway additionally suggest a role of sEH in regulating
Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences circulating cholesterol concentrations and subsequent coronary heart disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in cholesterol biosynthesis and is efficacious in lowering CHD events ...
Technology Transfer Automated Retrieval System (TEKTRAN)
is a target for drug discovery, and many drugsssuch as Lipitor (used to lower cholesterol), Fosamax (used in isoprenoid biosynthesis are drug targets. For example, the most widely prescribed drug, Lipitor, targets cho
All amaranth varieties contain tocotrienols and squalene compounds which are known to affect cholesterol biosynthesis. Therefore, in the present study, the influence of dietary supplementation of whole seed, popped, and milled amaranth and amaranth oil on cholesterogenesis was studied in 6-wk-old female chickens. Serum total ...
To examine whether cytosolic acetyl-CoA hydrolase in rat liver is involved in regulation of cholesterol biosynthesis, we investigated the alteration of the enzyme activity under conditions of stimulation (cholestyramine treatment) and suppression [cholesterol feeding, a potent competitive inhibitor of microsomal ...
BackgroundNormal post-squalene cholesterol biosynthesis is important for mammalian embryonic development. Neonatal mice lacking functional dehydrocholesterol ?7-reductase (Dhcr7), a model for the human disease of Smith-Lemli-Opitz syndrome, die within 24 hours of birth. Although they have a number of biochemical and structural ...
A load of ubiquinone-9 given by hypodermic injection for 2 days in a dosage of 200 mg/kg lowers liver cholesterol content in rats. There is also a decrease in cholesterol esters. The intensity of cholesterol biosynthesis, measured according to uptake of 2-/sup 14/C-acetate, is depressed to one-third to one-fifth. ...
Insig-1 and Insig-2 are regulatory proteins that restrict the cholesterol biosynthetic pathway by preventing proteolytic activation of SREBPs and by enhancing degradation of HMG-CoA reductase. Here, we created Insig-double-knockout (Insig-DKO) mice that are homozygous for null mutations in Insig-1 and Insig-2. After 18.5 days of development, 96% of Insig-DKO embryos had ...
Insig-1 and Insig-2 are regulatory proteins that restrict the cholesterol biosynthetic pathway by preventing proteolytic activation of SREBPs and by enhancing degradation of HMG-CoA reductase. Here, we created Insig�double-knockout (Insig-DKO) mice that are homozygous for null mutations in Insig-1 and Insig-2. After 18.5 days of development, 96% of Insig-DKO embryos had ...
Serum lipid abnormalities were evaluated in 53 patients (40 men and 23 women) undergoing maintenance hemodialysis and 22 non-uremic patients (14 men and 8 women) with the nephrotic syndrome. Serum levels of cholesterol, triglycerides and high-density-lipo...
Ehrlichia chaffeensis and Anaplasma phagocytophilum are agents of human monocytic and granulocytic ehrlichioses, respectively. They are extremely sensitive to mechanical stress and are pleomorphic gram-negative bacteria. Membrane incorporation of cholesterol from the eukaryotic host is known to be essential for other fragile and pleomorphic bacteria and mycoplasmas that lack a ...
Blood Pressure; Heart Rate and Rhythm Disorders; Hypoglycemia; Lactate; Nitrate; Cholesterol (Total and HDL); Abnormality in Fetal Heart Rate or Rhythm, Unspecified as to Episode of Care
ClinicalTrials.gov
The biosyntheses of cholesterol from acetate and mevalonate were determined in rat liver homogenates that were prepared and incubated in buffers containing varying concentrations of phosphate. Relatively little acetate or mevalonate was incorporated into cholesterol in the absence of added phosphate. When phosphate was added, there was an increase in ...
An automated fluorescence microscopy assay using a non-toxic cholesterol-binding protein, toxin domain 4 (D4) (Shimada et al. Eur J Biochem 269: 6195 (2002)), was developed, in order to identify chemical compounds modifying intracellular cholesterol metabolism and distribution. Using this method, we screened a library of 1056 compounds and identified 35 ...
To study the pathogenesis of cholesterol gallstones, we fed 24 adult male prairie dogs a high cholesterol, egg yolk diet. 13 control animals received a cholesterol-free diet. All animals fed the egg yolk diet formed multiple gallstones in 2-6 months' time. These stones contained cholesterol, 77�14% by dry weight. ...
Recent findings suggest that alterations in cholesterol homeostasis might be associated with Huntington's disease (HD). Although alterations in cholesterol content have been detected in cell models and several rodent models of HD, it is currently unclear what the potential mechanisms underlying cholesterol perturbations are. ...
Side chain oxysterols are cholesterol derivatives thought to signal the abundance of cell cholesterol to homeostatic effector proteins. Here, we investigated how plasma membrane (PM) cholesterol might regulate 27-hydroxycholesterol (HC) biosynthesis in cultured fibroblasts. We showed that PM ...
An important aspect of catalysis by cholesterol oxidase (3?-hydroxysteroid oxidase) is the nature of its association with the lipid bilayer that contains the sterol substrate. Efficient catalytic turnover is affected by the association of the protein with the membrane as well as the solubility of the substrate in the lipid bilayer. In this review, the binding of ...
As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, ...
Cholesterol is an essential molecule for the life cycle of the hepatitis C virus (HCV). This review focuses on the roles of cholesterol in HCV infection and introduces HCV events related to cholesterol metabolism and applications for cholesterol metabolism as a therapeutic target. HCV appears to alter host lipid ...
Normal haematological values and cholesterol values (total, HDL-cholesterol, LDL-cholesterol) were determined in free-living Herring and Great Black-backed Gulls, taking into account species, age and sex. These figures were then used as a basis of comparison with findings on birds with apparent clinical ...
The effects of freeze-dried soya milk (SM) and Bifidobacterium-fermented soya milk (FSM) on plasma and liver lipids, and faecal steroid excretion were estimated in hamsters fed on a cholesterol-free or cholesterol-enriched diet. Hamsters fed on the cholesterol-free diet containing 300 g FSM/kg had lower levels of plasma VLDL + LDL ...
The in vitro biosynthesis of isoprene from DL-mevalonate in the cytosolic fraction of rat liver is described. Evidence is provided suggesting a nonenzymatic formation of isoprene from isopentenyl pyrophosphate and/or dimethylallyl pyrophosphate. Furthermore, the data establish an alternate fate of the mevalonate carbon skeleton providing the first evidence that breath isoprene ...
Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to ...
Assisted reproduction technologies (ART) include in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and are common treatments for infertility. Although generally successful, ART warrant further investigations due to emerging perinatal issues, especially low birth weight. Herein we extend our previous work demonstrating higher steroid clearance in murine ART placentas by ...
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive condition involving craniofacial and central nervous system malformations with occasional holoprosencephaly (HPE). It is caused by a defect in the 7-dehydrocholesterol (7-DHC) reductase, the enzyme catalyzing the last step of cholesterol biosynthesis. Treatment of pregnant rats with inhibitors ...
Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are ...
The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid disorders. N,N-dimethyl-3�-hydroxycholenamide (DMHCA) is a steroidal ligand of LXRs that ...
The Smith�Lemli�Opitz syndrome (SLOS) is an autosomal recessive disease presenting with multiple congenital anomalies, caused by a defect in cholesterol biosynthesis that results in abnormally elevated levels of 7-dehydrocholesterol (7DHC). Progressive retinal degeneration has been demonstrated in a rat model of SLOS, which is ...
Cholesterol is essential for neuroactive steroid production, growth of myelin membranes, and normal embryonic and fetal development. It also modulates the oxytocin receptor, ligand activity and G-protein coupling of the serotonin-1A receptor. A deficit of cholesterol may perturb these biological mechanisms and thereby contribute to autism spectrum ...
The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome caused by an inborn error of cholesterol biosynthesis. The RSH/SLOS phenotypic spectrum is broad; however, typical features include microcephaly, ptosis, a small upturned nose, micrognathia, postaxial polydactaly, second and third ...
Hyperinsulinemia is known to promote the progression/worsening of insulin resistance. Evidence reveals a hidden cost of hyperinsulinemia on plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP(2))-regulated filamentous actin (F-actin) structure, components critical to the normal operation of the insulin-regulated glucose transport system. Here we delineated whether increased glucose ...
Vascular calcification impairs vessel compliance and increases the risk of cardiovascular events. We previously found that liver X receptor (LXR) agonists, which regulate intracellular cholesterol homeostasis, augment PKA agonist- or high phosphate-induced osteogenic differentiation of vascular smooth muscle cells (VSMC). Since cholesterol is an integral ...
Cholesterol is one of the major components of membrane lipids. Adjustment of the membrane cholesterol balance is, therefore, pivotal in the maintenance of cellular homeostasis. Cholesterol biosynthesis and uptake are tightly regulated at the transcriptional level through a negative feedback control. The ...
The distribution and movement of cholesterol were studied in granulosa cells from the ovaries of estrogen-stimulated hypophysectomized immature rats cultured in serum-free medium. Plasma membrane cholesterol was distinguished from intracellular cholesterol with cholesterol oxidase, an enzyme that converts cell ...
Cholesterol is reportedly abundant in the endocrine secretory granule (SG) membrane. In this study, we examined the involvement of cholesterol biosynthesis intermediates and inhibitors in insulin secretion and SG formation mechanisms. There are two routes for the supply of cholesterol to the cells: one via de novo ...
Suicidal behavior and mood disorders are one of the world's largest public health problems. The biological vulnerability for these problems includes genetic factors involved in the regulation of the serotonergic system and stress system. The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates the body's response to stress and has complex interactions with brain ...
Introduction Rapid development of novel technologies, including large-scale genome and proteome analysis, produces simultaneous quantitative dynamic characteristics of the most biological molecules in a cell. Mathematical modeling of gene networks dynamics; analysis of their normal and pathological states; diagnostics of mutations in biological systems; study of the evolution have become topical ...
Cholesterol inhibits isopentenyl ?3,?2-isomerase of Mycoplasma laidlawii in an apparently competitive fashion. The conversion of mevalonic acid to isopentenyl pyrophosphate is slightly stimulated. Organisms grown in the presence of mevalonic-2-14C acid contain small amounts of radio-label in nucleic acid and ...
The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of {sup 3}H{sub 2}O and ({sup 14}C)mevalonate into digitonin-precipitable sterols with time of incubation in vitro and a lack of ...
Background and aims: Newly synthesised cholesterol contributes poorly to biliary lipid secretion but may assume greater importance when the rate limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is upregulated. As this occurs in the gall stone susceptible C57L/J inbred mouse, we employed two cholesterol biosynthesis ...
The effects of squalestatin 1 on rat brain and liver homogenates and on Chinese hamster ovary tissue culture cells have been investigated. This compound effectively inhibits squalene biosynthesis in a highly selective manner. Cytoplasmic farnesyl pyrophosphate and geranylgeranyl pyrophosphate synthases are not affected, which is also the case for microsomal ...
BackgroundCholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% ...
In eukaryotes, intracellular cholesterol homeostasis and trafficking are tightly regulated. Certain bacteria, such as Anaplasma phagocytophilum, also require cholesterol; it is unknown, however, how this cholesterol-dependent obligatory intracellular bacterium of granulocytes interacts with the host cell ...
Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. We previously demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid accumulation and liver injury. The liver plays an important role in cholesterol ...
The asymptomatic, chronic carrier state of Salmonella enterica serovar Typhi occurs in the bile-rich gallbladder and is frequently associated with the presence of cholesterol gallstones. We have previously demonstrated that salmonellae form biofilms on human gallstones and cholesterol-coated surfaces in vitro and that bile-induced biofilm formation on ...
It is generally believed that cholesterol homoeostasis in the brain is both linked to and impacted by Alzheimer's disease (AD). For example, elevated levels of cholesterol in neuronal plasma and endosome membranes appear to be a pro-amyloidogenic factor. The recent observation that the C-terminal transmembrane domain (C99, also known as the beta-C-terminal ...
SummaryIt is generally believed that cholesterol homoeostasis in the brain is both linked to and impacted by Alzheimer�s disease (AD). For example, elevated levels of cholesterol in neuronal plasma and endosome membranes appears to be a pro-amyloidogenic factor. The recent observation that the C-terminal transmembrane domain (C99, also known as the ...
Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. ...
Cholesterol biosynthesis is among the most intensely regulated processes in biology. Synthetic rates vary over hundreds of fold depending on the availability of an external source of cholesterol. Studies of this feedback regulatory process have a rich history. The field began 75 years ago when Rudolf Schoenheimer measured ...
The epidermis is a dynamic system whose metabolic activity is regulated in large part by the integrity of the permeability barrier. This barrier resides in the stratum corneum and comprises a unique 2-compartment system of structural protein-enriched corneocytes embedded in a lipid-enriched intercellular matrix. Lipid extraction or metabolic imbalances, such as essential fatty acid deficiency, ...
The central hypothesis we are addressing is that inhibition of mammary carcinogenesis by n-3 polyunsaturated fatty acids (PUFAs) can be accounted for by their inhibitory effect on the cholesterol biosynthesis (mevalonate) pathway. In Task 3, we have shown...
The central hypothesis we are addressing is that inhibition of mammary carcinogenesis by n-3 polyunsaturated fatty acids(PUFAs)can be accounted for by their inhibitory effect on the cholesterol biosynthesis (mevalonate) pathway. In Task 1, we have shown t...
Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthesis pathway, it requires sterols as essential nutrients. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. Because sterol metabolism in ...
The serum lipoproteins of five patients with abetalipoproteinemia (ABL) were separated by ultracentrifugation and then analyzed either intact or after delipidation. It is concluded that ABL is a disorder affecting all serum lipoprotein classes. Whether the abetalipoproteinemia previously described and noted in the current studies is related to or independent of the ...
Leishmania parasites, despite being able to synthesize their own sterols, acquire and accumulate significant amounts of cholesterol through low density lipoprotein (LDL) particle endocytosis. The role of this system in Leishmania amazonensis promastigotes under pharmacological pressure by sterol biosynthesis inhibitors (SBIs) was investigated. First, thin ...
BACKGROUND: Several researchers have reported that Chinese adults may have a greater chronic disease burden than Whites, especially at lower body mass index (BMI) levels. OBJECTIVES: To compare the incidence of lipid abnormalities in Chinese (n=5303), White (n=10,752) and Black (n=3408) middle-aged adults and the effect of BMI on these incidences. METHODS: Data were from the ...
Background:Coronary artery disease (CAD) is the most common cause of sudden death, none and death of men and women over 20 years of age. The aim of the study was to know if there is any linear correlation between oxidants and abnormal lipid profile parameters in CAD.Materials and Methods:The present study includes 42 known CAD cases (age = 41�75 years) and 33 age- and ...
Chronic cholesterol feeding has been shown to produce abnormal plasma lipoproteins in a variety of experimental animals and man. In order to explore the role of the intestine in the production of these abnormal lipoproteins, rats were chronically fed a diet containing 1% cholesterol and 10% olive oil and were ...
The obligate intracellular protozoan Toxoplasma gondii resides within a specialized parasitophorous vacuole (PV), isolated from host vesicular traffic. In this study, the origin of parasite cholesterol was investigated. T. gondii cannot synthesize sterols via the mevalonate pathway. Host cholesterol biosynthesis remains unchanged after ...
Epidemiological, animal, and cellular studies suggest that abnormalities in cholesterol metabolism are important in the pathogenesis of Alzheimer�s disease (AD), potentially by increasing amyloid-? (A?) peptide levels. Accumulation of A? in the brain is suggested to play a key role in the neurodegenerative processes by triggering the hyperphosphorylation ...
The enzyme oxidosqualene:lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S),25-epoxycholesterol, a ligand activator of the liver ...
The Smith-Lemli-Opitz syndrome (SLOS; also known as "RSH syndrome" [MIM 270400]) is an autosomal recessive multiple malformation syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this ...
ER-119884 and E5700, novel arylquinuclidine derivatives developed as cholesterol-lowering agents, were potent in vitro growth inhibitors of both proliferative stages of Leishmania amazonensis, the main causative agent of cutaneous leishmaniasis in South America, with the 50% inhibitory concentrations (IC(50)s) being in the low-nanomolar to subnanomolar range. The compounds ...
Perfluorooctanoate, a peroxisome proliferator-activated receptor alpha (PPAR?) agonist, has the potential to lower testosterone levels as a result of testicular toxicity. To elucidate the mechanism and impact of PPAR? on this reproductive toxicity, ammonium perfluorooctanoate (APFO) at doses of 0, 1.0 (low) mg/kg/day, or 5.0 (high) mg/kg/day was orally given daily to 129/sv wild-type (mPPAR?), ...
ER-119884 and E5700, novel arylquinuclidine derivatives developed as cholesterol-lowering agents, were potent in vitro growth inhibitors of both proliferative stages of Leishmania amazonensis, the main causative agent of cutaneous leishmaniasis in South America, with the 50% inhibitory concentrations (IC50s) being in the low-nanomolar to subnanomolar ...
Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation syndrome resulting from mutations of the 7-dehydrocholesterol reductase gene (DHCR7). During de novo cholesterol biosynthesis, DHCR7 catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. A clinical diagnosis of SLOS is confirmed biochemically by the presence ...
The effect of copper deficiency on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme regulating cholesterol biosynthesis, was investigated in the rat. Male weanling rats were fed synthetic diets containing copper levels of 6.5 ppm (adequate), 1.6 ppm (marginal) and 0.9 ppm (deficient) for 7 wks. At sacrifice plasma lipids, ...
Proctocolectomy modifies the enterohepatic circulation and activity of bacterial enzymes depending on the structure of the stoma and function of the terminal ileum. We evaluated in our comparative study effects of different colectomy constructions on cholesterol metabolism. Levels of lipoprotein cholesterol and triglycerides, noncholesterol sterols, and ...
Amaranth was an important ancient grain and has current nutritional potential, being high in protein, fiber, lysine, magnesium, calcium, and squalene. Limited, inconsistent evidence demonstrates amaranth grain or oil can lower cholesterol in animal models. In the present study, hamsters received hypercholesterolemic diets consisting of a control, 10 or 20% Amaranthus cruentus ...
Selected species of the order Peronosporales, which are unable to epoxidize squalene and thus synthesize sterols, are able to metabolize exogenous cycloartenol to lanosterol and in some organisms to fucosterol, ergosterol, and cholesterol. Lanosterol was less effectively utilized but some ergosterol and cholesterol were yielded. Fucosterol was very ...
OBJECTIVETo explore the prevalence of lipid abnormalities and their relationship with albumin excretion and microalbuminuria in adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODSThe study population comprised 895 young subjects with type 1 diabetes (490 males); median age at the baseline assessment was 14.5 years (range 10�21.1), and median diabetes duration was ...
We describe the rudolph mouse, a mutant with striking defects in both central nervous system and skeletal development. Rudolph is an allele of the cholesterol biosynthetic enzyme, hydroxysteroid (17-beta) dehydrogenase 7, which is an intriguing finding given the recent implication of oxysterols in mediating intracellular Hedgehog (Hh) signaling. We see an ...
The function of lysosomes relies on the ability of the lysosomal membrane to fuse with several target membranes in the cell. It is known that in lysosomal storage disorders (LSDs), lysosomal accumulation of several types of substrates is associated with lysosomal dysfunction and impairment of endocytic membrane traffic. By analysing cells from two severe neurodegenerative LSDs, we observed that ...
The well established inverse relation of high density lipoprotein cholesterol (HDL) and the risk of coronary artery disease was tested in a cross-sectional group of 572 asymptomatic aircrew members who were being screened for risk of coronary artery disease. A battery of tests was performed, including determinations of fasting serum cholesterol, HDL ...
Proper cholesterol transport is essential to healthy cellular activity and any abnormality can lead to several fatal diseases. However, complete understandings of cholesterol homeostasis in the cell remains elusive, partly due to the wide variability in reported values for intra- and intermembrane cholesterol ...
Although maternal-fetal cholesterol transfer may serve to compensate for insufficient fetal cholesterol biosynthesis under pathological conditions, it may have detrimental consequences under conditions of maternal hypercholesterolemia leading to preatherosclerotic lesion development in fetal aortas. Maternal ...
Cardiovascular disease (CVD) is the Nation's leading killer for both men and women among all racial and ethnic groups. Development and progression of CVD is linked to the presence of risk factors such as hyperlipidemia, hypertension, obesity, and diabetes mellitus. It is known that cholesterol is an indicator of increased risk of heart attack and stroke. Low-density ...
