Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We screened 42 Korean traditional tea plants to determine the inhibitory effect of acetylcholinesterase and attenuation of toxicity induced by amyloid-beta peptide, which were related to the treatment of Alzheimer's disease (AD). The methanolic extract from Artemisia asiatica among tested 42 tea plants, showed the highest inhibitory effect (48%) on acetylcholinesterase in vitro. The methanolic extract was further separated with n-hexane, chloroform, and ethyl acetate of water, in order. The chloroform solubles, which were high in inhibitory effect of acetylcholinesterase, were repeatedly subjected to open column chromatography on silica gel. From the highest inhibitory fraction (78%) on acetylcholinesterase, the single compound was obtained by the Sep-Pak Cartridge (C18: reverse phase column). This compound was found to react positively on Dragendorff's reagent (potassium bismuth iodide), which typically reacted with the alkaloid. This compound was purified by HPLC (mu-bondapack C18 reverse phase column: 3.9 x 150 mm). The IC50 (the concentration of 50% enzyme inhibition) value of this compound was 23 micrograms/ml and the inhibitory pattern on acetylcholinesterase was mixed with competitive/non-competitive type. We examined the effects of this compound on toxicity induced by A beta (25-35) in rat pheochromocytoma PC12 cells. Pretreatment of the PC12 cells for 2 h with an alkaloid of Artemisia asiatica (1200 microg/ml) reduced the toxicity induced by A beta. This study demonstrated that an alkaloid of Artemisia asiatica, which was metabolized to small molecule in digestive tract and then could pass through the blood-brain barrier, appeared to be an acetylcholinesterase inhibitor with a blocker of neurotoxicity induced by A beta in human brain causing Alzheimer's disease.
Mol Cells 2000 Jun 30
PMID:Inhibitory effect of Artemisia asiatica alkaloids on acetylcholinesterase activity from rat PC12 cells. 1090 Nov 62

In this study total lipid (TL) content and the fatty acid composition changes in the liver of red deer stags (n=35) and fallow deer bucks (n=19) were examined at various reproductive stages. Samples were taken from mature red deer stags in the rut (September), in the post-rut (October), at the end of the rut (November) and after sexual activity had ceased (January). Sampling from mature fallow bucks was performed in the pre-rut (early October), in the rut (November) and after the reproduction period (January). The results obtained indicated significant (P<0.001) fatty degeneration of the liver in the males at the rutting season. At that time the TL concentration (x+/-S.D. in wet weight) was 156+/-40 g/kg in the red deer stags and 405+/-46 g/kg in the fallow bucks. Subsequent to the rutting season this value decreased to 47+/-15 g/kg by November in the red deer stags and to 51+/-3 g/kg by January in the fallow bucks. Significant changes were also observed in the fatty acid composition of the liver lipids, determined by gas chromatography. Liver samples collected during the rutting season from both red deer stags and fallow bucks showed higher (P<0.001) total proportions of monounsaturated fatty acids and lower (P<0.001) weight percentages of polyunsaturated fatty acids than those taken in January. In comparison with January the liver samples taken in September from red deer stags showed significantly higher (P<0.001) proportions of fatty acids C14:0, C15:0 and C:16:1, and significantly lower (P<0. 001) proportions of C18:0, C20:4 (n-6) and C22:5 (n-3). The proportions of C14:0, C15:1, C17:1 and C18:3 (n-3) in the liver samples taken in November from fallow bucks were higher (P<0.001), while the proportions of C18:0 and C20:4 (n-6) were lower (P<0.001) than those measured prior to rutting (in October) or after the rut (in January).
Comp Biochem Physiol A Mol Integr Physiol 2000 May
PMID:Liver total lipids and fatty acid composition of shot red and fallow deer males in various reproduction periods. 1090 58

Human serum albumin (HSA) is an abundant plasma protein that is responsible for the transport of fatty acids. HSA also binds and perturbs the pharmacokinetics of a wide range of drug compounds. Binding studies have revealed significant interactions between fatty acid and drug-binding sites on albumin but high-resolution structural information on ligand binding to the protein has been lacking. We report here a crystallographic study of five HSA-fatty acid complexes formed using saturated medium-chain and long-chain fatty acids (C10:0, C12:0, C14:0, C16:0 and C18:0). A total of seven binding sites that are occupied by all medium-chain and long-chain fatty acids have been identified, although medium-chain fatty acids are found to bind at additional sites on the protein, yielding a total of 11 distinct binding locations. Comparison of the different complexes reveals key similarities and significant differences in the modes of binding, and serves to rationalise much of the biochemical data on fatty acid interactions with albumin. The two principal drug-binding sites, in sub-domains IIA and IIIA, are observed to be occupied by fatty acids and one of them (in IIIA) appears to coincide with a high-affinity long-chain fatty acid binding site.
J Mol Biol 2000 Nov 10
PMID:Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin. 1106 71

The study revealed the presence of plasmalogens in the low density lipoprotein (LDL) and high density lipoprotein (HDL) of the fish. The composition of the plasmalogen in the carp plasma LDL phospholipids was 0.94 and 0.23% in the HDL; the LDL phospholipids in the rainbow trout were 0.44% and the HDL was 0.18%. Aldehydes from the plasmalogen were derivatized with dansylhydrazides and separated by high performance liquid chromatography (HPLC). Their presence was detected using a fluorescence detector. Hexadecanal (C16: 0), octadecanal (C18: 0) and octadecenal (C18: 1) were determined to be the major components in the carp and rainbow trout.
Comp Biochem Physiol A Mol Integr Physiol 2000 Nov
PMID:Detection of plasmalogen from plasma low density lipoprotein and high density lipoprotein in carp, Cyprinus carpio, and rainbow trout, Oncorhynchus mykiss. 1111 43

We studied the effects of wintertime undernutrition on the fatty acid composition of bone marrow triacylglycerols (TAGs) of legs in freely-ranging reindeer calves (<1 year) and adult hinds by comparing reindeer in poor condition slaughtered in February with reindeer in good condition slaughtered in October. Significant reductions were found in the proportions of the major monounsaturated fatty acid, or oleic acid, and in linoleic and alpha-linolenic acids in the femur TAGs of the undernourished reindeer as compared with the reindeer in good condition. As a result of these changes, the unsaturation index (UI) of the femur TAGs was reduced by 11% both in the calves and hinds. Similarly, there were also significant reductions in the proportions of oleic and linoleic acid in the metatarsal TAGs in the undernourished hinds, but only in linoleic acid in the calves. The UI of the metatarsal TAGs of the hinds was reduced by 7%, but that of the calves remained unchanged. The results suggest selective mobilization of oleic acid and the principal C18-polyunsaturated fatty acids from bone marrow TAGs in the undernourished reindeer during winter. These changes decrease the unsaturation degree of bone marrow fats, and, if advanced, may impair their fluidity and the functioning of the legs in the cold.
Comp Biochem Physiol B Biochem Mol Biol 2001 Jan
PMID:The effect of wintertime undernutrition on the fatty acid composition of leg bone marrow fats in reindeer (Rangifer tarandus tarandus L.). 1116 5

The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the last step of the biosynthesis of sex steroids from cholesterol. This family of steroidogenic enzymes constitutes an interesting target in the control of the concentration of estrogens and androgens. Among the isoforms of 17beta-HSD, type II preferentially catalyzes the oxidation of estradiol (E(2)), testosterone (T), dihydrotestosterone (DHT), and 20alpha-dihydroprogesterone (20alpha-DHP). Based on structure-activity relationship studies, we have developed steroidal spirolactones as inhibitors of type II 17beta-HSD using different steroid nuclei: a C18-steroid (lactones 1 and 10), an antiestrogenic nucleus (lactone 2), and a C19-steroid (lactone 28). We know these inhibitors are selective for type II 17beta-HSD as no or only weak inhibition was observed for types I and III. They also have no proliferative (androgenic) activity on androgen sensitive (AR(+)) Shionogi cells whereas their proliferative (estrogenic) activity on estrogen sensitive (ER(+)) ZR-75-1 cells depends on the nature of the steroid nucleus. Lactones 1 and 10 are weak estrogens, while lactones 2 and 28 do not exert estrogenic activity, in fact lactone 2 is an antiestrogen. Lactones 1, 2, 10 and 28 were also tested in an identical assay with a series of enzyme substrates, C19-steroid diols, and known inhibitors, for the oxidation of testosterone and estradiol into androstenedione and estrone, respectively. From this comparative study, the best inhibitors of type II 17beta-HSD (oxidase activity) were identified, but none of them were clearly more potent than the hydroxylated (reduced) forms of enzyme substrates, E2, T, and DHT. Such inhibitors remain, however, useful tools to, (1) further elucidate the role of type II 17beta-HSD, and (2) regulate the level of active estrogens, androgens and progesterone.
Mol Cell Endocrinol 2001 Jan 22
PMID:Inhibitors of type II 17beta-hydroxysteroid dehydrogenase. 1116 20

Kinetic parameters of chicken and rat lipoprotein lipase (LPL) were determined in the incubation in vitro with various monoacid triacylglycerol emulsion and plasma lipoproteins. In rat- and chicken-LPL there is an inverse relationship between the hydrolytic rate by both LPL and the increased acyl-chain unsaturation of monoacid triacylglycerol; C18:1>C18:2>C18:3. The rat LPL catalyzed hydrolysis of saturated monoacid triaclyglycerol increased with an increase of chain length as C16>C14>C12, whereas in chicken LPL hydrolytic rate of C12 was higher than C14 and C16 triaclyglycerol. Vmax of rat- and chicken-LPL for chylomicron and VLDL were higher but apparent Km for those were lower than other lipoproteins. In chicken, Vmax and apparent Km of LPL for VLDL were almost the same as those for chylomicron, whereas in rat, Vmax of LPL for VLDL was twice that of chylomicron with the same apparent Km. The chicken and rat VLDL with different particle size prepared by Bio-Gel A50 gel chromatography were similarly hydrolyzed by LPL, while the hydrolysis of small chicken-chylomicron particles was inclined to be higher than that of the large particles. These results show species differences between chickens and rats in the substrate specificity of LPL.
Comp Biochem Physiol A Mol Integr Physiol 1998 Feb
PMID:Species differences in substrate specificity of lipoprotein lipase purified from chickens and rats. 1124 4

The cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus, were found to contain minor amounts of novel wax esters, in addition to the major components, hydrocarbons. The wax esters ranged in carbon number from C19 to C31 and consisted of esters of both odd- and even-numbered alcohols and acids. Each wax ester with a given carbon number eluted at several different retention times indicating possible methyl branching in either the fatty acid or alcohol moiety, or in both moieties. Each eluting peak of wax esters consisted of a mixture of wax esters of the same carbon number in which the fatty acid moiety ranged from C8 to C18, and the alcohol moiety ranged from C8 to C17. Some wax esters were largely found on the head indicating they may be of a glandular origin. The hydrocarbons consisted of: n-alkanes, C23 to C33; odd-numbered n-alkenes, C27 to C35; and the major components, methyl-branched alkanes, C26 to over C49. Notable components of the methyl-branched alkanes were 2-methyltriacontane, and the novel trimethylalkanes with a single methylene between the first and second branch points, 13,15,19-trimethylhentriacontane and 13,15,21-trimethyltritriacontane.
Comp Biochem Physiol B Biochem Mol Biol 2001 Mar
PMID:Novel wax esters and hydrocarbons in the cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus. 1125 May 53

Deletion of the yeast gene ACB1 encoding Acb1p, the yeast homologue of the acyl-CoA-binding protein (ACBP), resulted in a slower growing phenotype that adapted into a faster growing phenotype with a frequency >1:10(5). A conditional knockout strain (Y700pGAL1-ACB1) with the ACB1 gene under control of the GAL1 promoter exhibited an altered acyl-CoA profile with a threefold increase in the relative content of C18:0-CoA, without affecting total acyl-CoA level as previously reported for an adapted acb1Delta strain. Depletion of Acb1p did not affect the general phospholipid pattern, the rate of phospholipid synthesis, or the turnover of individual phospholipid classes, indicating that Acb1p is not required for general glycerolipid synthesis. In contrast, cells depleted for Acb1p showed a dramatically reduced content of C26:0 in total fatty acids and the sphingolipid synthesis was reduced by 50-70%. The reduced incorporation of [(3)H]myo-inositol into sphingolipids was due to a reduced incorporation into inositol-phosphoceramide and mannose-inositol-phosphoceramide only, a pattern that is characteristic for cells with aberrant endoplasmic reticulum to Golgi transport. The plasma membrane of the Acb1p-depleted strain contained increased levels of inositol-phosphoceramide and mannose-inositol-phosphoceramide and lysophospholipids. Acb1p-depleted cells accumulated 50- to 60-nm vesicles and autophagocytotic like bodies and showed strongly perturbed plasma membrane structures. The present results strongly suggest that Acb1p plays an important role in fatty acid elongation and membrane assembly and organization.
Mol Biol Cell 2001 Apr
PMID:Depletion of acyl-coenzyme A-binding protein affects sphingolipid synthesis and causes vesicle accumulation and membrane defects in Saccharomyces cerevisiae. 1129 13

When human platelets are chilled below 22 degrees C, they spontaneously activate, a phenomenon that severely limits their storage life. It has previously been proposed that there is a correlation between cold-induced platelet activation and passage of the membranes through a liquid-crystalline to gel phase transition. Because animal models are essential for developing methods for cold storage of platelets, it is necessary to investigate such a correlation in animal platelets. In this work, horse platelets were used as a model, and it was found that cold-induced morphological activation is related to the lipid phase transition. Using fluorescence microscopy with the lipophilic fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil-C18), and Fourier transform infrared spectroscopy (FTIR), it was found that lipid phase separation occurs during cooling and low temperature storage. Furthermore, removal of cholesterol from the plasma membrane also induced a phase separation, possibly between specific phospholipid classes. Steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-DPH (TMA-DPH) were compared in cells and multilamellar vesicles (MLV) composed of platelet lipids. Cholesterol depletion led to a decrease in the fluorescence anisotropy of the two probes, which can be explained by changes in the order of the phospholipid molecules. In addition, the lipid composition and fatty acid profile of the cellular phospholipids were determined. Based of the similarities between horse and human platelets, it is suggested that horse platelets may be used as a model for studying cold-stored platelets. The results are discussed in relation to the possible role of phase separation during cell signalling.
Mol Membr Biol
PMID:Lipid phase separation correlates with activation in platelets during chilling. 1130 74


<< Previous 1 2 3 4 5 6 7 8 9 10