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)

[14C]-labelled palmitic acid (PA), oleic acid (OA), linoleic (LA) and arachidonic (AA) acids were transferred from macrophages (M phi) to lymphocytes (LY) when equal numbers of the two cell types were co-cultured. The relative degree and amounts of the fatty acids transferred from M phi to LY are as follow: AA (368.57 +/- 21.62) = OA (274.52 +/- 15.41) > LA (42.11 +/- 8.31) = PA (36.53 +/- 2.45). The transfer units are nmol/10(10) M phi/10(10) LY and the values are mean +/- SEM for 7 experiments. The [14C]-radioactivity transferred was mainly directed to the phospholipid fraction of the lymphocytes (85% by PA, 86% by LA, 83% by OA and 79% by AA). In the same order as above, phosphatidylcholine was the phospholipid moiety most heavily labelled (82% by PA, 71% by LA, 66% by OA and 47% by AA). The amount of [14C]-radioactivity transferred to stimulated lymphocytes of thioglycollate treated animals remained unchanged for LA, PA and AA but reduced for OA (71%). The significance of these observations for the immune functions of the cells and resolution of the question of whether some of the [14C]-isotope transfer involves a component of exchange or is unequivocally net fatty acid mass transfer are still being investigated.
Biochem Mol Biol Int 1997 Dec
PMID:Evidence for the transfer in culture of [14C]-labelled fatty acids from macrophages to lymphocytes. 941 23

This study assessed the possibility that the intraovarian insulin-like growth factor I (IGF-I) system interacts with the intraovarian interleukin-1 (IL-1) system, the central role of which has been the subject of increasing attention. To this end, whole ovarian dispersates from immature rats were cultured for 48 h in the absence or presence of IGF-I or IGF-binding protein-3 (IGFBP-3), with or without IL-1beta. Cellular RNA content was subjected to a solution hybridization, RNase protection assay with gel-purified [32P]-UTP-labelled antisense riboprobes for rat IL-1beta, type I IL-1 receptor (IL-1R) and secretory phospholipase A2 (sPLA2). PLA2 activity in conditioned media was assayed by measuring the release of [3H]-labelled palmitic acid from the sn-2 position of [3H]-labelled phosphatidylcholine dipalmitoyl (PCDP) substrate. Treatment with IGF-I resulted in a significant (P< 0.01) decrease in type I IL-1R transcripts (an effect which was reversed by co-treatment with IL-1beta), was without effect on IL-1beta transcripts, and significantly (P < 0.05) increased sPLA2 gene expression (an effect which was further enhanced by co-treatment with IL-1beta). Treatment with IGF-I resulted in a significant increase in extracellular PLA2 activity over untreated control. These observations suggest that IGF-I may down-regulate ovarian IL-1 action by decreasing type I IL-1R gene expression, while up-regulating sPLA2 gene expression and activity. These findings are consistent with a role for IGF-I in suppressing IL-1 actions while promoting the generation of prostaglandins. It is tempting to speculate that IGF-I, an intraovarian regulator concerned with promoting folliculogenesis, may be also entwined with priming the prostaglandin-producing potential in anticipation of subsequent ovulation.
Mol Hum Reprod 1997 Dec
PMID:Insulin-like growth factor I affects the intraovarian interleukin-1 system: evidence for suppression of type I interleukin-1 receptor expression and enhancement of secretory phospholipase A2 expression and activity. 946 54

A simple and fast method for the determination of the multi-site binding of fenoprofen (FP) to human serum albumin (HSA) has been developed by utilizing microdialysis sampling techniques combined with high performance liquid chromatography (HPLC). The drug and protein were mixed in different molar ratios in 0.067 Mol potassium phosphate buffer, pH 7.4, and incubated at 37 degrees C in a water-bath. Then the microdialysis probe was put in the FP-HSA solution and sampled at the perfusion rate of 1 microL/min. The concentrations of FP in microdialysates were determined by the reversed-phase high performance liquid chromatography. Relative recovery (R) was also determined in vitro on similar condition, R is about 56.03 +/- 1.11% (n = 3). Fenoprofen was found to bind to two classes of sites, the association constant (K1) and the number of the binding sites on primary binding sites of a HSA molecule (n1) for fenoprofen are 3.4 x 10(5)/M and 2.5, respectively, and those for secondary binding are 1.0 x 10(4)/M and 10.0, respectively. The competitive interaction of ibuprofen (IP) and palmitic acid with fenoprofen to HSA were also studied, both compounds significantly decrease the binding degree of fenoprofen to HSA.
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PMID:Multi-site binding of fenoprofen to human serum albumin studied by a combined technique of microdialysis with high performance liquid chromatography. 947 Sep 66

We have tried to approach the nature of the last common ancestor to Haemophilus influenzae and Escherichia coli and to determine how each bacterium could have diverged from this putative organism. The approach used was exhaustive analysis of the homologous proteins coded by genes present in these bacteria, using as criteria for sequence relatedness an alignment of at least 80 amino acid residues and a PAM distance (number of accepted point mutations per 100 residues separating two sequences) below 250. Evolutionarily significant similarities were found between 1,345 H. influenzae proteins (85% of the total genome) and 3,058 E. coli. proteins (75% of the total genome), many of them belonging to families of various sizes (from 666 doublets to 35 large groups of more than 10 members). Nearly all the genes found by this approach to be duplicated in both bacteria were already duplicated in their last common ancestor. This was deduced from (1) the comparison of the respective distributions of evolutionary distances between orthologs (genes separated only by speciation events) and paralogs (genes duplicated in the same genome) and (2) the analysis of the phylogenetic trees reconstructed for each family of paralogs containing at least two members belonging to each bacterium. The distributions of the different categories of homologs show a significant loss of paralogous genes in H. influenzae (reduction proportional to the genome size), of many sequences which are still present in one copy in E. coli, and of some entire gene families. Phylogenetic trees also confirmed this recent loss of paralogous genes in H. influenzae. Thus, the genome size of the last common ancestor of these two bacteria would have been close to that of present-day E. coli, and the evolution of H. influenzae toward a parasitic life led to an important decrease in its genome size by some mechanism of streamlining. During this recent evolution, the memory of the gene order present in the last common ancestor has been blurred, but a few short conserved chromosomal fragments can still be detected in present-day E. coli and H. influenzae.
Mol Biol Evol 1998 Jan
PMID:The evolutionary relationships between the two bacteria Escherichia coli and Haemophilus influenzae and their putative last common ancestor. 949 1

Fatty acids have been shown to regulate the expression of mRNA for both lipogenic and glycolytic enzymes in rat liver. The role of fatty acids in the regulation of carnitine palmitoyltransferase (CPT) I and II activity in tumour cells was investigated. The polyunsaturated fatty acids, gamma-linolenic and arachidonic acid, caused 60-70% inhibition of tumour cell CPT I activity and 45-50% inhibition of [14C]-palmitic acid oxidation to 14CO2. These effects were blocked by the cyclooxygenase inhibitor, indomethacin. Prostaglandins E1 and E2 caused marked inhibition of both CPT I and CPT II activity and inhibition of cell proliferation. Prostaglandin E2 production by tumour cells was increased in the presence of arachidonic acid and inhibited when indomethacin was present. The proliferation of the HT29 cell line was unaffected as was its CPT I and II activity by both fatty acids and prostaglandins. CPT I mRNA expression was not inhibited by fatty acids, indeed it increased-in the presence of arachidonic acid and prostaglandin E1. These results strongly suggest that polyunsaturated n-6 fatty acids are able, via prostaglandin products, to regulate the CPT activity of certain tumour cells. This may have a considerable impact on mitochondrial beta-oxidation and cellular metabolism of fatty acids, reflected in the marked inhibition of cell proliferation by these fatty acids.
Biochem Mol Biol Int 1998 Jan
PMID:Regulation of tumour cell fatty acid oxidation by n-6 polyunsaturated fatty acids. 950 57

This study is designed to investigate whether substrate preference in the myocardium during the neonatal period and hypoxia-induced stress is controlled intracellularly or by extracellular substrate availability. To determine this, the effect of exogenous L-carnitine on the regulation of carbohydrate and fatty acid metabolism was determined during cardiac stress (hypoxia) and during the postnatal period. The effect of L-carnitine on long chain (palmitate) and medium chain (octonoate) fatty acid oxidation was studied in cardiac myocytes isolated from less than 24 h old (new born; NB), 2 week old (2 week) and hypoxic 4 week old (HY) piglets. Palmitate oxidation was severely decreased in NB cells compared to those from 2 week animals (0.456+/-0.04 vs. 1.207+/-0.52 nmol/mg protein/30 min); surprisingly, cells from even older hypoxic animals appeared shifted toward the new born state (0.695+/-0.038 nmol/mg protein/30 min). Addition of L-carnitine to the incubation medium, which stimulates carnitine palmitoyl-transferase I (CPTI) accelerated palmitate oxidation 3 fold in NB and approximately 2 fold in HY and 2 week cells. In contrast, octanoate oxidation which was greater in new born myocytes than in 2 week cells, was decreased by L-carnitine suggesting a compensatory response. Furthermore, oxidation of carbohydrates (glucose, pyruvate, and lactate) was greatly increased in new born myocytes compared to 2 week and HY cells and was accompanied by a parallel increase in pyruvate dehydrogenase (PDH) activity. The concentration of malonyl-CoA, a potent inhibitor of CPTI was significantly higher in new born heart than at 2 weeks. These metabolic data taken together suggest that intracellular metabolic signals interact to shift from carbohydrate to fatty acid utilization during development of the myocardium. The decreased oxidation of palmitate in NB hearts probably reflects decreased intracellular L-carnitine and increased malonyl-CoA concentrations. Interestingly, these data further suggest that the cells remain compliant so that under stressful conditions, such as hypoxia, they can revert toward the neonatal state of increased glucose utilization.
Mol Cell Biochem 1998 Mar
PMID:Regulation of carbohydrate and fatty acid utilization by L-carnitine during cardiac development and hypoxia. 954 35

The nodulation protein NodF of Rhizobium shows 25% identity to acyl carrier protein (ACP) from Escherichia coli (encoded by the gene acpP). However, NodF cannot be functionally replaced by AcpP. We have investigated whether NodF is a substrate for various E. coli enzymes which are involved in the synthesis of fatty acids. NodF is a substrate for the addition of the 4'-phosphopantetheine prosthetic group by holo-ACP synthase. The Km value for NodF is 61 microM, as compared to 2 microM for AcpP. The resulting holo-NodF serves as a substrate for coupling of malonate by malonyl-CoA:ACP transacylase (MCAT) and for coupling of palmitic acid by acyl-ACP synthetase. NodF is not a substrate for beta-keto-acyl ACP synthase III (KASIII), which catalyses the initial condensation reaction in fatty acid biosynthesis. A chimeric gene was constructed comprising part of the E. coli acpP gene and part of the nodF gene. Circular dichroism studies of the chimeric AcpP-NodF (residues 1-33 of AcpP fused to amino acids 43-93 of NodF) protein encoded by this gene indicate a similar folding pattern to that of the parental proteins. Enzymatic analysis shows that AcpP-NodF is a substrate for the enzymes holo-ACP synthase, MCAT and acyl-ACP synthetase. Biological complementation studies show that the chimeric AcpP-NodF gene is able functionally to replace NodF in the root nodulation process in Vicia sativa. We therefore conclude that NodF is a specialized acyl carrier protein whose specific features are encoded in the C-terminal region of the protein. The ability to exchange domains between such distantly related proteins without affecting conformation opens exciting possibilities for further mapping of the functional domains of acyl carrier proteins (i. e., their recognition sites for many enzymes).
Mol Gen Genet 1998 Apr
PMID:Functional analysis of an interspecies chimera of acyl carrier proteins indicates a specialized domain for protein recognition. 960 87

Salmonella typhimurium apeR mutations lead to overproduction of an outer membrane-associated N-acetyl phenylalanine beta-naphthyl ester-cleaving esterase that is encoded by the apeE gene (P. Collin-Osdoby and C. G. Miller, Mol. Gen. Genet. 243:674-680, 1994). This paper reports the cloning and nucleotide sequencing of the S. typhimurium apeE gene as well as some properties of the esterase that it encodes. The predicted product of apeE is a 69.9-kDa protein which is processed to a 67-kDa species by removal of a signal peptide. The predicted amino acid sequence of ApeE indicates that it is a member of the GDSL family of serine esterases/lipases. It is most similar to a lipase excreted by the entomopathogenic bacterium Photorhabdus luminescens. The Salmonella esterase catalyzes the hydrolysis of a variety of fatty acid naphthyl esters and of C6 to C16 fatty acid p-nitrophenyl esters but will not hydrolyze peptide bonds. A rapid diagnostic test reported to be useful in distinguishing Salmonella spp. from related organisms makes use of the ability of Salmonella to hydrolyze the chromogenic ester substrate methyl umbelliferyl caprylate. We report that the apeE gene product is the enzyme in Salmonella uniquely responsible for the hydrolysis of this substrate. Southern blot analysis indicates that Escherichia coli K-12 does not contain a close analog of apeE, and it appears that the apeE gene is contained in a region of DNA present in Salmonella but not in E. coli.
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PMID:The apeE gene of Salmonella typhimurium encodes an outer membrane esterase not present in Escherichia coli. 965 91

Distances between amino acids were derived from the polar requirement measure of amino acid polarity and Benner and co-workers' (1994) 74-100 PAM matrix. These distances were used to examine the average effects of amino acid substitutions due to single-base errors in the standard genetic code and equally degenerate randomized variants of the standard code. Second-position transitions conserved all distances on average, an order of magnitude more than did second-position transversions. In contrast, first-position transitions and transversions were about equally conservative. In comparison with randomized codes, second-position transitions in the standard code significantly conserved mean square differences in polar requirement and mean Benner matrix-based distances, but mean absolute value differences in polar requirement were not significantly conserved. The discrepancy suggests that these commonly used distance measures may be insufficient for strict hypothesis testing without more information. The translational consequences of single-base errors were then examined in different codon contexts, and similarities between these contexts explored with a hierarchical cluster analysis. In one cluster of codon contexts corresponding to the RNY and GNR codons, second-position transversions between C and G and transitions between C and U were most conservative of both polar requirement and the matrix-based distance. In another cluster of codon contexts, second-position transitions between A and G were most conservative. Despite the claims of previous authors to the contrary, it is shown theoretically that the standard code may have been shaped by position-invariant forces such as mutation and base content. These forces may have left heterogeneous signatures in the code because of differences in translational fidelity by codon position. A scenario for the origin of the code is presented wherein selection for error minimization could have occurred multiple times in disjoint parts of the code through a phyletic process of competition between lineages. This process permits error minimization without the disruption of previously useful messages, and does not predict that the code is optimally error-minimizing with respect to modern error. Instead, the code may be a record of genetic process and patterns of mutation before the radiation of modern organisms and organelles.
J Mol Evol 1998 Jul
PMID:On error minimization in a sequential origin of the standard genetic code. 966 91

The secretion of pathogenicity factors by Salmonella typhimurium is mediated by a type III secretion system that includes an outer membrane protein of the secretin family. Related secretins are also required for f1 phage assembly and type II secretion. When the C-terminal 43 amino acids of the S. typhimurium secretin InvG are added to f1 pIV, the chimeric f1 pIV-'InvG43 protein becomes dependent on the co-expression of another gene, invH, for function in phage assembly. [3H]-palmitic acid labelling, globomycin sensitivity and density gradient flotation were used to demonstrate that InvH is an outer membrane lipoprotein that is processed by signal peptidase II. A complex between chimeric f1 pIV-'InvG43 and InvH was demonstrated in vivo. InvH was shown to be required for the proper localization of InvG in the outer membrane and for the secretion of the virulence factor SipC. These results suggest that InvH and InvG are part of the functional outer membrane translocation complex in type III secretion systems.
Mol Microbiol 1998 Jun
PMID:The Salmonella typhimurium InvH protein is an outer membrane lipoprotein required for the proper localization of InvG. 968 Feb 24


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