Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbohydrates, particularly disaccharides, have been shown to accumulate in organisms as protective solutes during periods of stress such as freezing and desiccation. Cholesterol and lipid derivatives containing the protective carbohydrates galactose or maltose, O-[11-(1-beta-D-galactosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-GAL), O-[11-(1-beta-D-maltosyloxy)-3,6,9-trioxaundecanyl]ol (TEC-MAL), and 14-(galactosyloxy)-N,N-dimethyl-O-(dipalmitoylphosphatidyl)- 6,9,12-trioxa-3- azoniatetradecanol (DP-GAL), have been synthesized to investigate the interaction of a protective carbohydrate moiety tethered to the 1,2-dipalmitoylphosphatidylcholine (DPPC) bilayer surface. Toward this goal, we have investigated the calorimetric and infrared spectroscopic behavior of mixtures of DPPC codried with these glycolipids. The synthetic glycolipids are shown to decrease significantly the main transition temperature (max Cp) of dry DPPC with a concomitant reduction in the cooperativity of the transition, as evidenced by a decrease in the enthalpy with increasing glycolipid. The decrease in transition temperature is shown to be related to chain melting monitored by the CH2 symmetric stretch frequency through the transition using FTIR. We also present evidence that the glycolipids interact with the interfacial region of DPPC, as shown by the decrease in the phosphate symmetric stretch intensity with increasing concentration of glycolipid. These observed effects are similar to the action of bulk protective sugars with DPPC; however, the concentration of glycolipid and the associated carbohydrate concentration needed to effect the observed changes are reduced compared to the quantity of bulk carbohydrate previously shown to give similar results with DPPC.
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PMID:Modification of dry 1,2-dipalmitoylphosphatidylcholine phase behavior with synthetic membrane-bound stabilizing carbohydrates. 152 Jul 23

A combination of two methods, polyacrylamide gel electrophoresis (PAGE) and neutron activation analysis (NAA), has been applied to solutions containing phosphoproteins for the purpose of protein quantification. The proteins were separated by molecular weight using PAGE, and then the whole gel was activated by neutron bombardment. Densitometric measurements of the developed bands from 32P, taken from autoradiographs of the activated gels, resulted in quantification of the phosphorus, and then the related protein. This PAGE/NAA method was applied to several phosphoprotein-containing materials, including commercial milk products and reference materials, i.e., IAEA A-11, milk powder, and SRM 1845, Cholesterol in Egg Powder.
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PMID:Application of polyacrylamide gel electrophoresis/neutron activation analysis for protein quantification. 170 87

Factors affecting the esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT E.C. 2.3.1.43) in native cold labelled substrates (human, rabbit, rat serum, plasma, VLDL, LDL depleted serum, rabbit intraocular fluids) repaired by use of ready-made 14C-cholesterol discs (Cholesterol kinetics LCAT-test, UVVVR, Czechoslovakia) were investigated. EDTA added to the serum during the cold incubation (18 h, 0 degrees C-4 degrees C) increased the rate of esterification due to elimination of Ca2+ ions. The similar stimulating effect was found in the presence of mercaptoethanol (ME) in the serum, while in the plasma already stimulated by EDTA no additional effect by ME could be noticed. Freezing and thawing did not affect the fractional esterification rate (FER-per cent of total serum unesterified cholesterol esterified per hour) in normolipidaemic sera, whereas in hyperlipidaemic sera, particularly those with high levels of VLDL, FER was stimulated. Esterification partially proceeded during the cold incubation of serum or plasma with 14C-cholesterol ready-to-use discs, attaining the values of about 0.3%/h and 2-6%/h, respectively, in human sera and in rabbit and rat sera. The starting level of esterification did not affect the linearity of LCAT reaction during warm incubation (30 min at 37 degrees C), neither was the absolute value of FER changed as compared with cold labelled sera with those inhibited by DTNB and reactivated by ME. Substantial LCAT activity was also detected in extremely diluted substrates--such as intraocular fluid collected from rabbits with induced uveitis or after preceding paracentesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors influencing the cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay. 294 8

Cholesterol and cholesteryl esters in human serum were determined by supercritical fluid chromatography on an inert ODS-silica gel column using supercritical carbon dioxide as a mobile phase without a modifier. Chromatograms were obtained by monitoring the eluent simultaneously with an FID and UV detector at the wavelength of 190 nm. The retention behavior of cholesterol and cholesteryl esters was investigated in terms of the density of CO2 mobile phase. The separation mode was found to be reversed phase, as in liquid chromatography. The amounts of cholesterol and cholesteryl esters extracted from human serum reference material (NIST SRM 909) were determined individually using cholesteryl laurate as an internal standard to give good agreement of total cholesterol with the value certified by NIST.
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PMID:Supercritical fluid chromatographic determination of cholesterol and cholesteryl esters in serum on ODS-silica gel column. 837 64

Mouse melanoma B16 cells are characterized by a high concentration of GM3 ganglioside, which has been identified as a melanoma-associated antigen and is present as a clustered microdomain organized with major signal transducers, c-Src, small G-protein (Rho A), and focal adhesion kinase (FAK), to form a "glycosphingolipid signaling domain" or "glycosignaling domain" (GSD) separable from cholesterol- and caveolin-enriched microdomain, "caveolae." Cholesterol-binding reagents, filipin and nystatin, disrupt the structure and function of caveolae, but have no effect on GSD function [Iwabuchi, K., et al. (1998) J. Biol. Chem. 273, 33766-33773]. In this study, we searched for compounds which disrupt the structure and function of GSD in B16 cells. Such compounds should have structural features analogous to those of GM3, destroy or reduce clustering of GM3 in GSD, and inhibit GM3-dependent adhesion and signaling. The simplest compound so far found with these properties is sialyl alpha2-->1 sphingosine (Sph). We describe the synthesis of this compound and its analogues, and their effects on GM3 expression pattern and GSD function, in comparison with effects of lyso-GM3 and other lyso compounds, in B16 cells. Incubation of B16 cells with 0.5-10 microM sialyl alpha2-->1 Sph or 1-5 microM lyso-GM3 reduced GM3 clustering and GM3-dependent adhesion, and inhibited adhesion-dependent cellular FAK activity. The c-Src activation response of GSD isolated from B16 cells was inhibited strongly by sialyl alpha2-->1 Sph. Substitution of the Sph amino group with a chloroacetyl or N,N-dimethyl group strongly reduced the inhibitory effect of sialyl alpha2-->1 Sph on GM3-dependent adhesion, FAK, and c-Src response. Other lyso compounds such as lyso-phosphatidylcholine, galactosyl-Sph (psychosine), and lactosyl-Sph at 0.5-10 microM did not show the same effect as sialyl alpha2-->1 Sph. Thus, adhesion coupled with signal transduction, initiated by clusters of GM3 in GSD, is blocked by sialyl alpha2-->1 Sph or lyso-GM3. Analogues with N-substitution of Sph in sialyl alpha2-->1 Sph, other lyso-phospholipids, and galactosyl- or lactosyl-Sph did not block such adhesion, coupled with activation of c-Src and FAK.
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PMID:Effect of synthetic sialyl 2-->1 sphingosine and other glycosylsphingosines on the structure and function of the "glycosphingolipid signaling domain (GSD)" in mouse melanoma B16 cells. 1070 95

A number of food-matrix reference materials (RMs) are available from the National Institute of Standards and Technology (NIST) and from Agriculture Canada through NIST. Most of these materials were originally value-assigned for their elemental composition (major, minor, and trace elements), but no additional nutritional information was provided. Two of the materials were certified for selected organic constituents. Ten of these materials (Standard Reference Material [SRM] 1,563 Cholesterol and Fat-Soluble Vitamins in Coconut Oil [Natural and Fortified], SRM 1,566b Oyster Tissue, SRM 1,570a Spinach Leaves, SRM 1,974a Organics in Mussel Tissue (Mytilus edulis), RM 8,415 Whole Egg Powder, RM 8,418 Wheat Gluten, RM 8,432 Corn Starch, RM 8,433 Corn Bran, RM 8,435 Whole Milk Powder, and RM 8,436 Durum Wheat Flour) were recently distributed by NIST to 4 laboratories with expertise in food analysis for the measurement of proximates (solids, fat, protein, etc.), calories, and total dietary fiber, as appropriate. SRM 1846 Infant Formula was distributed as a quality control sample for the proximates and for analysis for individual fatty acids. Two of the materials (Whole Egg Powder and Whole Milk Powder) were distributed in an earlier interlaboratory comparison exercise in which they were analyzed for several vitamins. Value assignment of analyte concentrations in these 11 SRMs and RMs, based on analyses by the collaborating laboratories, is described in this paper. These materials are intended primarily for validation of analytical methods for the measurement of nutrients in foods of similar composition (based on AOAC INTERNATIONAL's fat-protein-carbohydrate triangle). They may also be used as "primary control materials" in the value assignment of in-house control materials of similar composition. The addition of proximate information for 10 existing reference materials means that RMs are now available from NIST with assigned values for proximates in 6 of the 9 sectors of the AOAC triangle. Five of these materials have values assigned for total dietary fiber-the first such information provided for materials available from NIST.
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PMID:Value assignment of nutrient concentrations in five standard reference materials and six reference materials. 1077 81

Standard Reference Material 968c Fat-Soluble Vitamins, Carotenoids, and Cholesterol in Human Serum provides certified values for retinal, delta-, gamma-, and alpha-tocopherol, trans- and total beta-carotene, and cholesterol in human serum. Values are also reported for 16 additional compounds including lutein, zeaxanthin, alpha- and beta-cryptoxanthin, lycopene, alpha-carotene, retinyl palmitate, and 25-hydroxyvitamin D. The certified values for the fat-soluble vitamins and carotenoids in SRM 968c were based on the agreement of results from the means of at least two liquid chromatographic methods used at the National Institute of Standards and Technology (NIST) and from the medians from an interlaboratory comparison study among institutions that participate in the NIST Micronutrients Measurement Quality Assurance Program. The assigned values for cholesterol in the SRM are the means of results obtained using the NIST definitive method, gas chromatography-isotope dilution mass spectrometry.
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PMID:Preparation and value assignment of Standard Reference Material 968c Fat-Soluble Vitamins, Carotenoids, and Cholesterol in Human Serum. 1124 33

Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in cell membranes that regulate phosphorylation cascades originating from membrane-bound proteins. In this study, we tested whether alteration of the cholesterol content of lipid rafts in prostate cancer (PCa) cell membranes affects cell survival mechanisms in vitro and in vivo. Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Balpha)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin- and PTEN-negative LNCaP PCa cells. Replenishing cell membranes with cholesterol reversed these inhibitory and apoptotic effects. Cholesterol also potentiated Akt activation in normal prostate epithelial cells, which were resistant to the apoptotic effects of simvastatin. Elevation of circulating cholesterol in SCID mice increased the cholesterol content and the extent of protein tyrosine phosphorylation in lipid rafts isolated from LNCaP/sHB xenograft tumors. Cholesterol elevation also promoted tumor growth, increased phosphorylation of Akt, and reduced apoptosis in the xenografts. Our results implicate membrane cholesterol in Akt signaling in both normal and malignant cells and provide evidence that PCa cells can become dependent on a cholesterol-regulated Akt pathway for cell survival.
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PMID:Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. 1577 12

Cell adhesion and spreading is a crucial step in the metastatic cascade of cancer cells, and interruption of this step is considered to be a logical strategy for prevention and treatment of tumor metastasis. Emodin is the major active component of the rhizome of Rheum palmatum L., with known anticancer activities. Here, we first found that emodin significantly inhibited cell adhesion of various human cancer cells. This inhibition was achieved through suppressing the recruitment of focal adhesion kinase (FAK) to integrin beta(1) as well as the phosphorylation of FAK followed by the decreased formation of focal adhesion complex (FAC). In understanding the underlying mechanisms, we found that emodin inhibited the lipid raft clustering and subsequent colocalization of integrin beta(1) and FAC proteins within lipid rafts. Lipid profile analysis revealed significant decrease of cholesterol and sphingolipids in raft fraction after emodin treatment. Cholesterol replenishment abolished the adverse effect of emodin on the translocation of integrin beta(1) and FAC proteins into the lipid raft fraction and cell adhesion. Therefore, data from this study provide novel evidence that emodin inhibits cell adhesion and spreading through disruption of the membrane lipid raft-associated integrin signaling pathway.
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PMID:Emodin inhibits tumor cell adhesion through disruption of the membrane lipid Raft-associated integrin signaling pathway. 1674 Jul 20

This retrospective cohort study conducted at the Durham Veterans Affairs Medical Center evaluated the effectiveness and safety of lipid-lowering therapy (LLT) in a HIV-infected population as compared with a general population with hyperlipidaemia. Fifty-three HIV-infected subjects who developed dyslipidaemia and 53 age-matched non-HIV-infected subjects receiving LLT were selected. Efficacy of LLT was assessed after three and six months. Non-HIV-infected subjects were more likely to achieve total cholesterol (TC) goals at three and six months (P = 0.045, P = 0.005) and triglyceride (TG) goals at six months (P = 0.017). Less than 45% of HIV-infected subjects met National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) goals at three or six months. While non-HIV-infected subjects were more likely to achieve TC and TG goals than HIV-infected subjects, overall achievement of NCEP III goals was poor. This result was likely due to treatment with inappropriately low doses of statins.
Int J STD AIDS 2007 Dec
PMID:A comparison of the effectiveness of lipid-lowering therapy between HIV- and non-HIV-infected subjects with hyperlipidaemia. 1807 21


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