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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cuticle of adult Brugia malayi is the organisms's major point of interaction with the mammalian host environment. We therefore undertook an investigation in order to define the lipid composition of this outermost layer of the parasite. The lipid class and fatty acid composition of the cuticle of adult Brugia malayi was examined by surface specific radioiodination, organic extraction, thin layer chromatography and gas chromatography. The data were compared with those derived from similar analyses of somatic preparations of the parasites. The composition of the cuticular lipid fraction was found to be highly unusual and distinct from that of the internal lipids. Cholesterol esters and wax esters were absent from the cuticular lipid fraction, which was however enriched in unesterified fatty acids. The major polar lipids in both cuticular and somatic preparations were phosphatidylcholine and phosphatidylethanolamine, but unusually high levels of lysophosphatidylethanolamine were observed in the cuticular extracts. Analyses of cuticular polar lipids indicated that there is an asymmetric distribution of the fatty acids in phosphatidylethanolamine, assuming that lysophosphatidylethanolamine is derived from deacylation of the former molecule in the cuticle. The major fatty acids in all lipid fractions examined were the 18-carbon, mono- and di-unsaturated type, while significant amounts of palmitic, palmitoleic, stearic and eicosatrienoic acids were also found. A highly unusual feature of the cuticular lipid fraction was that it contained large amounts of a novel polar lipid species which, on exposure to atmospheric oxygen, degraded to a hydrophobic and a hydrophilic moiety. This polar lipid was absent from the somatic preparations. The data are discussed in terms of the possible resistance or susceptibility of the parasite to reactive oxygen species.
Mol Biochem Parasitol 1996 Jun
PMID:Identification and composition of lipid classes in surface and somatic preparations of adult Brugia malayi. 881 81

We investigated the relationship between the development of hypercholesterolemia in rabbits and cholesteryl ester transfer protein (CETP) activity secretion by their perfused livers. Two inbred strains of rabbits were compared which differ markedly in their hypercholesterolemic response to dietary cholesterol. Feeding a high-cholesterol (0.3%) diet, increased plasma and liver cholesterol level in the two strains, the increments being 15 mM and 30 mumol/g greater in the hyperresponders, respectively. The high-cholesterol diet caused an about 2-fold increased hepatic secretion of CETP activity, but there was no difference between the two rabbit strains. Feeding a lower amount of dietary cholesterol (0.08%) also caused higher cholesterolemic (2 mM) and hepatocholesterolic (28 mumol/g) responses in hyper- than in hyporesponsive rabbits. The activity of hepatic CETP secretion was not increased by the low-cholesterol diet, and there was no difference between hypo- and hyperresponsive rabbits. Cholesterol feeding increased plasma CETP activity by 90% in both rabbit strains, but there was no difference between the strains. Our combined data suggest that with increasing plasma cholesterol levels hepatic CETP secretion may be increased in a parabolic manner, reaching its maximum rate for before plasma cholesterol concentrations are maximal. There were no differences in hepatic CETP activity secretion of plasma CETP activity levels between the genetically different strains of hypo- and hyperresponsive rabbits.
Comp Biochem Physiol B Biochem Mol Biol 1996 Aug
PMID:CETP activity in liver perfusates and plasma from rabbits hypo- or hyperresponsive to dietary cholesterol. 884 May 15

Human sperm become responsive to inducers of the acrosome reaction when they are washed free of seminal plasma and incubated in an appropriate medium. Previous work has shown that cholesterol-enriched medium prevents sperm from becoming responsive to the inducer, progesterone. Sperm that were incubated 24 hr in cholesterol-enriched medium and then treated with progesterone showed no evidence of membrane fusion, indicating that cholesterol acts at a stage before the earliest morphological change. Inhibition of acrosomal responsiveness by cholesterol was reversible. Among other sterols reported in mammalian sperm, desmosterol and cholesterol sulfate also inhibited sperm from becoming responsive, but cholesterol palmitate did not. Our results support a model in which sperm unesterified cholesterol, or a molecule in equilibrium with it, suppresses acrosomal responsiveness. Cholesterol-enriched medium also prevented sperm from becoming responsive to the calcium/proton exchanging ionophore, ionomycin, suggesting that cholesterol's effect may be, at least in part, at a point in the signal transduction pathway subsequent to the rise in intracellular-free calcium.
Mol Reprod Dev 1996 Oct
PMID:Effect of cholesterol and other sterols on human sperm acrosomal responsiveness. 891 79

In order to define the substrate binding site of human cytochrome P-450(scc) in the vicinity of the 3beta-hydroxyl group of cholesterol, we have tested the ability of the cytochrome to cleave the side chain of a range of cholesterol esters and cholesterol methyl ether. Using a Tween-20 detergent reconstituted system we found that cholesterol sulphate could undergo side-chain cleavage with the same turnover number (kcat) as that for cholesterol, but with a higher Km. Cholesterol methyl ether underwent side-chain cleavage to pregnenolone methyl ether with kcat and Km values 30% of those for cholesterol. Cholesterol fatty acid esters with acyl chain lengths of up to four carbons were able to undergo side-chain cleavage with Km values similar to those for cholesterol, but kcat values only 12-23% of those for cholesterol. Turnover numbers decreased as the acyl group length increased beyond four carbons, although some activity was still detected with cholesterol palmitate as substrate. Analysis of bovine cytochrome P-450(scc) revealed that it could also cleave the side chain of acyl and sulphate esters of cholesterol. This study indicates that the substrate binding site of cytochrome P-450(scc) in the vicinity of the 3beta-hydroxyl group is larger than previously believed.
J Steroid Biochem Mol Biol 1996 Aug
PMID:Side-chain cleavage of cholesterol esters by human cytochrome P-450(scc). 891 88

The effects of two cell-permeable cyclic AMP analogues, 8-chloro cyclic AMP (8-Cl cAMP) and 8-(4-chlorophenylthio) cyclic AMP (8-CPT cAMP), on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis were compared in cultured rat and hamster hepatocytes. Cholesterol esterification, as measured by the incorporation of [3H]oleate into cholesteryl ester, was increased by 58-88% by the analogues in rat hepatocytes and by 33-43% in hamster cells. The response in rat hepatocytes, however, was observed after a relatively short incubation time (28% increase after 1 hr), whereas that in hamster cells required a longer period (36% after 12 hr) to become apparent. The activity of the cytosolic neutral cholesteryl ester hydrolase in rat hepatocytes was also stimulated by both cyclic AMP analogues (31-37%, but the microsomal activity was unaffected. In hamster hepatocytes, however, microsomal cholesteryl ester hydrolase activity was increased (47-80%) in the presence of 8-Cl cAMP or 8-CPT cAMP. Bile acid synthesis was increased by 8-CPT cyclic AMP in rat cells (approximately 25%) but was unchanged by both analogues in hamster hepatocytes. These results indicate significant differences in the way in which cholesterol metabolism responds to cyclic AMP in cultured rat and hamster hepatocytes.
Comp Biochem Physiol B Biochem Mol Biol 1996 Jan
PMID:Comparison of the effects of cyclic AMP analogues on cholesterol metabolism in cultured rat and hamster hepatocytes. 893 53

Cholesterol side-chain cleavage cytochrome P450 (CYP11A; P450scc) gene expression is regulated by gonadotropins via cAMP in the ovary and by ACTH via cAMP in adrenal cortical cells. Previously, we have characterized a response element located at -118 to -101 bp in the 5'-flanking region of the bovine P450scc gene required for cAMP-stimulated transcription in both mouse adrenocortical Y1 cells and bovine ovarian cells in primary culture. It was shown that this region contains a binding site for the transcription factor Sp1. Deletion of this sequence abolished cAMP-stimulated transcription in both Y1 cells and bovine ovarian luteal cells. Another sequence element located at -57 to -32 bp upstream from the transcription initiation site, which is highly conserved in CYP11A of other species, contains the motif TAGCCTTG, similar to the consensus binding site of steroidogenic factor-1, SF-1 (or Ad4-BP), but in the inverted orientation. In the present study, gel shift analysis using nuclear extracts of either Y1 cells or bovine luteal cells demonstrated that the sequence between -57 and -32 bp bound SF-1. A mutation of the SF-1-binding site that abolished binding of the nuclear protein to DNA reduced markedly the basal transcription of the reporter gene as well as the responsiveness to cAMP, when the mutated fragments containing the region from -186 to +12 bp were cloned into a luciferase construct and transfected into mouse adrenal Y1 cells and bovine luteal cells. The role of SF-1 in P450scc transcription was further confirmed by transactivation of the -186/+12Luc construct employing an SF-1 expression vector after transfection into nonsteroidogenic COS-1 cells. In addition, results obtained employing a double mutation of the Sp1- and SF-1-binding sites, and from a construct containing both Sp1 and SF-1 elements upstream of the CYP11A TATA box, indicated that Sp1 and SF-1 function cooperatively in the transactivation of the bovine CYP11A promoter in both bovine luteal cells and Y1 cells. Finally, a mammalian two-hybrid system was employed to demonstrate that Sp1 and SF-1 can associate in vivo. These results establish that basal and cAMP-stimulated activity of the bovine P450scc promoter in both Y1 cells and bovine luteal cells requires the combined action of at least two transcription factors, Sp1 and SF-1.
Mol Endocrinol 1997 Feb
PMID:Steroidogenic factor 1 (SF-1) and SP1 are required for regulation of bovine CYP11A gene expression in bovine luteal cells and adrenal Y1 cells. 901 60

Heparin has been shown to stimulate angiogenesis in the border zones surrounding infarcted myocardium. Matrix metalloproteinases (MMP), which are involved in extracellular matrix (ECM) organization, have also been shown to be activated. Cholesterol is required for receptor signaling in the plasma membrane, but a role of MMPs for cholesterol in ECM remodeling has not yet been shown. To examine whether heparin and cholesterol induce MMP and tissue inhibitor of metalloproteinase (TIMP) in human heart fibroblast (HHF) cells, confluent HHF cells were treated with cholesterol (100 microM) or heparin (20 microM). MMP activity was measured using zymography and TIMP was measured by Western blot analysis. The number of HHF cells, measured by a hemocytometer, increased after heparin or cholesterol treatment. Gelatinase A (MMP-2) activity increased in heparin treated cells, and the TIMP-1 level increased in cholesterol-treated cells. Based on Northern blot analysis, we observed that both MMP-1 and MMP-2 were induced at the gene transcription level by heparin and that TIMP-1 was induced by cholesterol. To examine whether the effects of heparin and cholesterol were due to Ca2+ mobilization, we carried out Ca2+ transient assays using FURA-2/AM as a fluorescence probe in HHF cells. Heparin induced a slow rise in the Ca2+ transient with a slow decay, and cholesterol induced a rapid rise with a slow reversal to the baseline calcium level. This suggested that the effect of heparin on Ca2+ release from HHF may be secondary to the receptor binding on the cell membrane but that cholesterol may have a direct effect. Protein kinase inhibitor and Ca2+-channel blocker have been shown to inhibit MMP expression. To examine whether the effect of heparin on MMP expression is mediated through the collagenase promoter activity, we carried out gel-shift assays using a 21-oligonucleotide analogue to the MMP-1 promoter sequence. Results suggested that the increase in MMP promoter activity by heparin is due to a specific transcription factor binding to MMP-1 promoter sequence. The effect of cholesterol on fibroblast cell proliferation is due in part to the tissue inhibitor. This study demonstrated the role of heparin and cholesterol in ECM remodeling and has implications for angiogenesis and athersclerosis, respectively.
J Mol Cell Cardiol 1997 Jan
PMID:Differential regulation of extracellular matrix metalloproteinase and tissue inhibitor by heparin and cholesterol in fibroblast cells. 904 53

The effects of chylomicron remnants (CR), beta-very-low-density-lipoproteins (beta-VLDL) and low-density-lipoproteins (LDL) on intracellular cholesterol synthesis and esterification in primary rabbit macrophages was determined by assaying for HMG-CoA reductase activity and cholesterol esterification. At physiological cholesterol concentrations, both CR and LDL inhibited cholesterol synthesis by almost 60% while beta-VLDL was less potent achieving only 30% inhibition. Cholesterol esterification rates were increased four-fold by CR and LDL, whereas beta-VLDL increased esterification 14 times above controls. Qualitatively, the effect of CR on cholesterol synthesis and esterification in rabbit macrophages differs from observations in transformed macrophage cells. Quantitatively, the enhanced rates of cholesterol esterification and weak inhibition of cholesterol synthesis following beta-VLDL uptake may explain why this lipoprotein rapidly induces foam cell formation in vitro.
Biochem Mol Biol Int 1997 Jan
PMID:Regulation of cholesterol synthesis and esterification in primary cultures of macrophages following uptake of chylomicron remnants. 904 32

Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing diet for 8 weeks. Blood cholesterol was lowered significantly by dietary curcumin in these diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids was also brought about by dietary curcumin in diabetic rats. In a parallel study, wherein diabetic animals were maintained on a high cholesterol diet, the extents of hypercholesterolemia and phospholipidemia were still higher compared to those maintained on control diet. Curcumin exhibited lowering of cholesterol and phospholipid in these animals also. Liver cholesterol, triglyceride and phospholipid contents were elevated under diabetic conditions. Dietary curcumin showed a distinct tendency to counter these changes in lipid fractions of liver. This effect of curcumin was also seen in diabetic animals maintained on high cholesterol diet. Dietary curcumin also showed significant countering of renal cholesterol and triglycerides elevated in diabetic rats. In order to understand the mechanism of hypocholesterolemic action of dietary curcumin, activities of hepatic cholesterol-7a-hydroxylase and HMG CoA reductase were measured. Hepatic cholesterol-7a-hydroxylase activity was markedly higher in curcumin fed diabetic animals suggesting a higher rate of cholesterol catabolism.
Mol Cell Biochem 1997 Jan
PMID:Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. 904 34

Tamoxifen, a non-steroidal anti-oestrogen, is used in the treatment of breast cancer, both receptor positive and negative tumours. It also possesses weak oestrogenic activity which forms the basis of this study. Tamoxifen (2 different dosages) was administered through diet (10 mg/kg diet and 20 mg/kg diet) to experimental atherosclerosis induced female rats to assess the effect of tamoxifen on plasma lipid levels, lipoprotein cholesterol level and on the activity of lipid metabolising enzymes. The plasma total lipid level was increased in atherosclerosis suffering animals compared to control animals with concomitant changes in the activity of lipid metabolising enzymes. HDL-cholesterol was decreased while LDL-cholesterol and VLDL-cholesterol were increased in the atherosclerosis induced group. Cholesterol and free cholesterol were decreased in tamoxifen treated groups while the other lipids show a moderate increase. HDL-cholesterol was increased but LDL-cholesterol was decreased in the tamoxifen treated groups. The higher dosage tamoxifen given group animals show significantly favourable results from therapy stand point when compared to diseased group.
Mol Cell Biochem 1997 Mar
PMID:Effect of tamoxifen on lipids and lipid metabolising marker enzymes in experimental atherosclerosis in Wistar rats. 906 89


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