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

A number of experimental paradigms have been used to demonstrate that NCAM, N-cadherin, and L1 stimulate axonal growth. The molecular basis of this response has been extensively studied and a range of agents that inhibit neurite outgrowth stimulated by the above CAMs, but not integrins, have now been identified. These studies pointed to the activation of a tyrosine kinase-PLCgamma cascade as being important for the neurite outgrowth responses stimulated by all three CAMs, and this was substantiated by the identification of agents that could activate the cascade and mimic the growth response. In this review we will suggest that the neurite growth response stimulated by these CAMs is mediated by activation of the fibroblast growth factor receptor (FGFR) in neurons and that this results in the recruitment and activation of PLCgamma via interactions of its SH2 domain with the activated receptor. In this context the key events downstream from activation of PLCgamma required for neurite growth appear to be the conversion of diacylglycerol (DAG) to arachidonic acid (AA) via DAG lipase activity, followed by an increased influx of calcium into the neurons. The evolutionary conservation of putative binding motifs between the above CAMs and the FGFR suggests that activation of the FGFR-PLCgamma cascade by the CAMs might involve a direct CAM-FGFR interaction. The identification of the binding motifs also allows for predictions to be made concerning whether other CAMs might directly interact with the FGFR.
Mol Cell Neurosci 1996 Aug
PMID:CAM-FGF Receptor Interactions: A Model for Axonal Growth 895 25

In order to perform studies on lipid mobilization in adult M. sexta, it is necessary to overcome the effects of starvation and handling, which both provoke an increase in hemolymph lipid concentration. When trehalose was injected into intact insects, a 35% decrease in the content of the diacylglycerol (DG)-rich hemolymph lipoprotein, low density lipophorin (LDLp) was observed within 30 min, but the level of LDLp returned to control values after 1 h. Decapitated insects exhibited 60% reduction in LDLp concentration and the levels remained low for at least 24 h. In contrast to intact insects, injection of trehalose into decapitated animals did not alter the LDLp concentration. After decapitation, the response to adipokinetic hormone (AKH) and the ability of the fat body to release DG into the hemolymph was maintained for at least 24 h. In decapitated insects, 6 pmol of AKH-stimulated measurable lipid mobilization and a near maximum response was obtained with 100 pmol of the hormone. The action of trehalose and AKH on the fat body triacylglycerol (TG)-lipase activity in decapitated animals was studied. Fat body homogenates from trehalose-treated insects exhibited a TG-lipase activity 40% lower than the control insects. Activation of fat body triacylglycerol-lipase was observed after injection of AKH, with the extent of activation ranging between 97 and 380% ten min after AKH injection. A time course study showed that the activation of the fat body triacylglycerol lipase preceded the increase in hemolymph LDLp concentration, suggesting that activation of the lipase initiates lipid mobilization. It is concluded that decapitated insects injected with trehalose is a very useful system for investigating the hormonal regulation of lipid mobilization in adult M. sexta.
Insect Biochem Mol Biol
PMID:The use of decapitated insects to study lipid mobilization in adult Manduca sexta: effects of adipokinetic hormone and trehalose on fat body lipase activity. 901 27

Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript lacking exons 1 and 2 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) in the ovaries of mature cyclic females and of immature rats treated with pregnant mare serum followed by human chorionic gonadotropin (hCG) to induce superovulation. By competitive RT-PCR the HL transcript was quantified. Low levels of HL mRNA were detected in ovaries of mature cyclic females and of immature rats. During superovulation HL mRNA was several fold higher than in mature cyclic rats and transiently increased to a maximum at 2 days after hCG treatment. Pulse-labelling of ovarian cells and ovarian slices with [35S]methionine followed by immunoprecipitation with polyclonal anti-HL IgGs showed de novo synthesis of a 47 kDa HL-related protein. Expression of the protein was transiently induced by gonadotropins with a peak at 2 days after hCG treatment. Induction of liver-type lipase activity occurred only after HL mRNA and synthesis of the HL-related protein had returned to pre-stimulatory levels. We conclude that in rat ovaries the HL gene is expressed into a variant mRNA and a 47 kDa protein. The expression of the HL gene in ovaries is inducible and precedes the expression of the mature, enzymatically active liver-type lipase.
Mol Cell Endocrinol 1997 Jan 03
PMID:Hepatic lipase gene expression is transiently induced by gonadotropic hormones in rat ovaries. 902 61

Molecular mechanisms of lipid synthesis and their controls in hepatic stellate cells are not known. We have previously proposed that, in contrast to other fat storing cells, hepatic stellate cells are not involved in energy storage, but they represent a particular cell population specialized in storage of lipid-soluble substances, the major one being probably retinol. In agreement with this hypothesis, induction of the lipocyte phenotype in stellate cells is not under the control of insulin, but responds to retinoids and other molecules that modify the gene expression program in these cells. In the present study we have monitored the activity of the two major enzymes involved in lipid synthesis during the induction of the lipocyte phenotype in hepatic stellate cells: glycerol-3-phosphate dehydrogenase (GPDH) that mediates the de novo lipid synthesis, and lipoprotein lipase that mediates incorporation of plasma lipids. In early stages of lipocyte induction, both pathways of lipid synthesis are activated. When lipocytes have already constituted the lipid droplets, lipoprotein lipase pathway is downregulated, while GPDH activity remains high. Adult liver has been reported to lack lipoprotein lipase, but under stress, lipase activity was detected around and at the surface of the intrahepatic vasculature. We have now shown that the lipase activity can be induced in the hepatic stellate cells, located in the Disse's space. The high lipoprotein lipase activity under acute induction of lipocyte phenotype, followed by the low activity under conditions of metabolic equilibrium, are in compass with the increased activity of this enzyme under stress, and its low activity in adult liver parenchyma under normal conditions.
Mol Cell Biochem 1997 Mar
PMID:Lipid metabolism during in vitro induction of the lipocyte phenotype in hepatic stellate cells. 906 91

Lipolysis is regulated by the presence of amphiphilic compounds such as bile salts and lecithin, which are adsorbed at the triglyceride-water interface and therefore influence the approach of water-soluble pancreatic lipase to its insoluble substrate (emulsified triglycerides). The partition of bile salts between the lipid and the aqueous phase is of prime importance in the expression of lipase activity. Lipase activity was determined as a function of different combinations of concentrations of deoxycholate and dipalmitoylphosphatidyl choline. From zeta-potential measurements, it is evident that lecithin affects the partition of bile salts, most probably by displacing deoxycholate molecules. Our results indicate that lecithin cannot be classified a priori as inhibitor or activator of pancreatic lipase. As an amphiphilic compound, lecithin exerts a synergistic effect with bile salts via the formation of mixed micelles. The final effect on lipolysis depends on the ratio of lecithin to bile salt: low ratios enhance enzyme activity, whereas high ratios lead to inhibition.
Comp Biochem Physiol B Biochem Mol Biol 1997 Jan
PMID:Combined effect of a lecithin and a bile salt on pancreatic lipase activity. 908 Jun 62

Tn10 and Tn9 from temperature-sensitive replicons RPI::Tn10 Rep is and RP1::Tn9 Rep ts and Tn5 from the "suicidal" vector pSUP5011 may integrate in the P. pseudomallei chromosome. Transposons induced auxotrophic mutations of different spectrum, depending on the strain, Tn element, and defects in the genes responsible for the mobility sign, function of some extracellular elements (lecithinase and lipase), hemolytic activity, and antigen 8 synthesis, which are considered as the potential factors of the pathogenicity of melioidosis agent. No secondary restructuring induced by Tn elements were detected in the domains adjacent to insertion sites. Plasmids RP1::Tn10 Rep ts and RP1::Tn9 Rep ts were stable in insertion mutant cells, mediating the variable TR-TS phenotype probably indicating that plasmid integration with the chromosome is unstable.
Mol Gen Mikrobiol Virusol 1997
PMID:[Insertion mutations in Pseudomonas pseudomallei genome induced by transposons Tn10. Tn9, and Tn5]. 908 81

Three cases are presented where modified chitins have been extensively administered to volunteers, as dressings for wounded soft and bone tissues, as anticholesterolemic dietary foods, and in the controlled delivery of anti-inflammatory drugs. The interactions of the modified chitins with human enzymes is critically examined. In the context of drug carrier resorption and wound healing, chitooligomers and monomers, generated by lysozyme, N-acetylglucosaminidase and human chitinase, activate macrophages and stimulate fibroblasts, respectively; the effects are production of smooth, vascularized and physiologically normal tissues. In the dietary food area, lipase, amylase, 3-hydroxy-3-methylglutaryl CoA reductase, glucokinase and the enzymes of prostaglandin synthesis are involved in the oral administration of chitosan: lipid adsorption is depressed mainly because of the physical form of the chitosan-lipid aggregates, which are unsuitable as substrates. When chitosan is used as a drug carrier, chitosan-drug complexes are present. The uniqueness of chitosan among polysaccharides is underlined in terms of susceptibility to enzymatic depolymerization, cationicity, supply of cell-activating oligomers, and supply of N-acetylglucosamine for rebuilding of other biopolymers. Advances in molecular recognition and biocompatibility are also presented.
Cell Mol Life Sci 1997 Feb
PMID:Human enzymatic activities related to the therapeutic administration of chitin derivatives. 911 1

The global activator GacA, a highly conserved response regulator in Gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and its role in cell-density-dependent gene expression was characterized. Mutational inactivation of gacA resulted in delayed and reduced formation of the cell-density signal N-butyryl-L-homoserine lactone (BHL), of the cognate transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhIR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhIR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase. However, the concentrations of another known cell-density signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always match BHL concentrations. A model accounting for these observations places GacA function upstream of LasR and RhIR in the complex, cell-density-dependent signal-transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL.
Mol Microbiol 1997 Apr
PMID:The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase. 915 18

Lipase enzymes have found increasingly widespread use, especially in biotransformation reactions in organic synthesis. Due to their efficiency and high enantioselectivity, they can be employed in a variety of reactions to carry out asymmetric hydrolyses, esterifications and transesterifications. However, the reasons for their stereospecificity have not been fully correlated with the enzyme structure. Employing molecular modelling techniques and existing experimental data, a transesterification reaction using Rhizomucor miehei lipase was studied. The results indicate that the major controlling factor for this reaction is hydrophobic in nature, providing support for previous literature hypotheses. In addition, computational experiments suggest that the origin of enantioselectivity is the formation of essential hydrogen bonds in and around the catalytic triad of active site residues. Only one enantiomer of the substrate is able to form these hydrogen bonds during the formation of the first tetrahedral transition state.
J Comput Aided Mol Des 1997 May
PMID:Molecular modelling studies of substrate binding to the lipase from Rhizomucor miehei. 926 52

The Serratia marcescens Lip exporter belonging to the ATP-binding cassette (ABC) exporter is known to be involved in signal peptide-independent extracellular secretion of a lipase and a metalloprotease. Although the genes of secretory proteins and their ABC exporters are usually all reported to be linked in several gram-negative bacteria, neither the lipase nor the protease gene is located close to the Lip exporter genes, lipBCD. A gene (slaA) located upstream of the lipBCD genes was cloned, revealing that it encodes a polypeptide of 100 kDa and is partially similar to the Caulobacter crescentus paracrystalline cell surface layer (S-layer) protein. The Lip exporter-deficient mutants of S. marcescens failed to secrete the SlaA protein. Electron micrography demonstrated the cell surface layer of S. marcescens. The S-layer protein was secreted to the cultured media in Escherichia coli cells carrying the Lip exporter. Three ABC exporters, Prt, Has and Hly systems, could not allow the S-layer secretion, indicating that the S. marcescens S-layer protein is strictly recognized by the Lip system. This is the first report concerning secretion of an S-layer protein via its own secretion system.
Mol Microbiol 1998 Mar
PMID:Serratia marcescens S-layer protein is secreted extracellularly via an ATP-binding cassette exporter, the Lip system. 953 84


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