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)

An exogenous [3H]triolein emulsion was hydrolyzed by intact cardiac myocytes with functional LPL located on the cell surface. This surface-bound LPL could be released into the medium when cardiac myocytes were incubated with heparin. Incubation of cardiac myocytes with VLDL, or the products of TG breakdown, oleic acid or 2-monoolein, did not increase LPL activity in the medium. However, incubation of cardiac myocytes with either VLDL or oleic acid for > 60 min did reduce heparin-releasable LPL activity. In the heart, this inhibitory effect of FFA could regulate the translocation of LPL from its site of synthesis in the cardiac myocyte to its functional site at the capillary endothelium.
Mol Cell Biochem 1992 Oct 21
PMID:Long term incubation of cardiac myocytes with oleic acid and very-low density lipoprotein reduces heparin-releasable lipoprotein lipase activity. 148 Jan 52

The murine gonadotropin-releasing hormone (Gnrh) locus has been mapped to mouse chromosome 14 using a mouse x Chinese hamster somatic cell hybrid panel. The equivalent human locus, known as luteinizing hormone-releasing hormone (LHRH), has been previously mapped to 8p21-8p11.2. Four other loci mapping to the human chromosome 8 short arm have been mapped to mouse chromosome 8; two of these (PLAT, GSR) lie proximal to LHRH, and two (LPL, DEF1) lie distal to LHRH. The localization of Gnrh, the murine homolog of LHRH, to mouse chromosome 14 therefore defines a hitherto unrecognized block of homology between man and mouse. Furthermore, it indicates that the region of homology between the human chromosome 8 short arm and mouse chromosome 8 is composed of two separate blocks.
Somat Cell Mol Genet 1991 Nov
PMID:The gonadotropin-releasing hormone (Gnrh) gene maps to mouse chromosome 14 and identifies a homologous region on human chromosome 8. 176 38

The heparin-induced secretion of LPL into the incubation medium of cardiac myocytes occurred in two phases: a rapid release (5-10 min), followed by a slower rate of release (10-60 min). Reducing the incubation temperature from 37 degrees C to 23 degrees C inhibited the slow phase of secretion, but had no effect on the rapid phase. Similarly, taxol, a microtubule-stabilizing drug, selectively reduced the slow phase of LPL release, without influencing the rapid release of LPL into the medium or cellular LPL activity. The rapid heparin-induced release of LPL probably occurs from sites that are at or near the cell surface, and so microtubules must participate in the intracellular transport of LPL from sites of synthesis and glycosylation to the surface binding sites. Heparin-releasable LPL could be resolved into two fractions by chromatography on con A-Sepharose; this pattern of elution was not affected by the prior treatment of cardiac myocytes with taxol.
Mol Cell Biochem
PMID:Effect of taxol on the heparin-induced secretion of lipoprotein lipase from cardiac myocytes. 257 Oct 74

Heparin (5 U/ml) induced the release of LPL into the incubation medium of cardiac myocytes isolated from adult rat hearts. The secretion of LPL occurred in two phases: a rapid release (5-10 min of incubation with heparin) that was independent of protein synthesis followed by a slower rate of release that was inhibited by cycloheximide. The rapid release of LPL induced by heparin likely occurs from sites that are at or near the cell surface. LPL secretion could also be stimulated by heparan sulfate and dermatan sulfate, but not by hyaluronic acid, chondroitin sulfate or keratan sulfate. Heparin-releasable LPL activity measured in short-term incubations represented a large fraction (40-50%) of the initial LPL activity associated with myocytes, but the fall in cellular LPL activity following heparin was less than the amount of LPL activity secreted into the incubation medium. This discrepancy was not due to latency of LPL in the pre-heparin cell homogenates, but in part could be due to a three-fold greater affinity of the heparin-released enzyme for substrate as compared to LPL in post-heparin myocyte homogenates.
Mol Cell Biochem 1988 Jan
PMID:Secretion of lipoprotein lipase from myocardial cells isolated from adult rat hearts. 337 75

By aligning nucleotide and amino acid sequences of lipoprotein lipase in eight species (man, pig, cow, sheep, mouse, rat, guinea-pig and chicken), we found that the main domains (catalytic, N-glycosylation and putative heparin binding sites) are well conserved. The longest identical amino acid chain was encoded by a sequence between the end of exon 2 and the beginning of exon 3, emphasizing the importance of this region which encodes the beta 5-loop of the active site, among other domains. Exon 10 is entirely untranslated in the seven mammals studied here and contains species-characteristic deletions, insertions or elements rich in A or A + T. In chicken, the beginning of exon 10 is translated. These eight previously unreported alignments could be a useful tool for further studies on LPL function.
Comp Biochem Physiol B Biochem Mol Biol 1995 Jul
PMID:Comparison of the cDNA and amino acid sequences of lipoprotein lipase in eight species. 761 63

Interleukin-11/adipogenesis inhibitory factor (IL-11/AGIF) inhibits adipogenesis and suppresses lipoprotein lipase (EC3.1.1.34, LPL) activity in adipocytes (1,2). We investigated the mechanism of suppression of LPL activity in 3T3-L1 adipocytes by IL-11/AGIF. Incubation of adipocytes with 50 ng/ml of IL-11/AGIF led to a 75% decrease in LPL activity within 8 hours, whereas LPL mRNA level decreased by less than 30%. The LPL synthesis, as judged by the incorporation of 35S-label into immunoprecipitable LPL, decreased at almost the same rate over the same time period as enzyme activity. The degradation rate was not significantly affected by IL-11/AGIF. These data suggest that regulation of the synthesis of the enzyme protein is at least one of the main steps in the suppression of LPL by IL-11/AGIF in 3T3-L1 adipocytes.
Biochem Mol Biol Int 1994 Mar
PMID:Regulation of lipoprotein lipase synthesis in 3T3-L1 adipocytes by interleukin-11/adipogenesis inhibitory factor. 803 20

Using the polymerase chain reaction (PCR) the frequency distributions of three short tandem repeats (STR) were investigated in five populations: North European, Cypriot, Pakistani, Gujarati and Vietnamese. Each STR is situated within an intron; the markers are in the genes for human coagulation factor XIII (4bp repeat), lipoprotein lipase (4bp repeat) and CD4 (5bp repeat). Population data were generated for each STR and allele frequencies calculated. A calculation of the level of population substructuring for the three systems was also made. The lipoprotein lipase STR data showed no evidence for population substructuring, but there was a significant level of substructuring in the other two systems. This initial pilot study demonstrates the need to validate each marker used for DNA profiling in different human populations, and that some markers (such as LPL) can be used with confidence in widely differing ethnic groups, while others (such as CD4 and F13A) may be of value in distinguishing sub-groups.
Hum Mol Genet 1993 Jul
PMID:Variation of short tandem repeats within and between populations. 836 38

We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.
Hum Mol Genet 1995 Sep
PMID:A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia. 854 37

The ligand-binding domain of low-density lipo-protein (LDL) is composed of seven 40-amino-acid repeats encoded by exons 2-6. Previous studies identified a missense mutation in codon 66 of exon 3, which resulted in the production of LDL receptor protein that is not processed to its mature form. In the current investigation, we documented the presence of two identical mutant LDL receptor alleles (Trp66-->Gly) in two familial hypercholesterolemia (FH) probands, II-1 and II-2, associated with markedly elevated plasma LDL cholesterol (17.22 +/- 0.78 and 11.95 +/- 0.24 mmol/liter, respectively). Functional assays of their fibroblast LDL receptor showed inefficient binding (39 and 50%), internalization (33 and 37%), and degradation (32 and 37%) compared with controls. The contribution of the apo B gene to variation in LDL levels was virtually eliminated given the normal ligand interaction with cell surface receptors and the absence of the mutation occurring in codon 3500 of the apo B gene. Similarly, the homozygous apo E3/E3 wildtype phenotype excluded any genetic contribution of apo E to the lipoprotein abnormalities. Furthermore, the LPL mutations commonly observed in French Canadians could not account for the observed lipid alterations. Several alterations in lipoprotein composition characterized VLDL, IDL, LDL, HDL2, and HDL3 fractions. Moreover, defective intestinal fat transport was observed in both probands (II-1 and II-2). Thus, the disturbance of lipoprotein concentration, composition, size, and metabolism may in part be related to the exon 3 mutation (Trp66-->Gly) of the LDL receptor gene. The biochemical phenotype was more severe in the father (I-1) than in the mother (I-2), and in the younger homozygous proband (II-1) than in the older (II-2). The greater severity was associated with a higher LDL cholesterol/HDL cholesterol ratio. Whether the differences between the two probands are due to polygenic factors or to a metabolic consequence of a major nonallelic trait is unknown. Nevertheless, the present biochemical findings stress the extent of the lipid abnormalities associated with homozygous FH and the importance of the phenotypic variability encountered even among subjects carrying the same mutation.
Biochem Mol Med 1997 Feb
PMID:Association of an exon 3 mutation (Trp66-->Gly) of the LDL receptor with variable expression of familial hypercholesterolemia in a French Canadian family. 906 82

The lipoyl domains of the dihydrolipoyl acyltransferase (E2p, E2o) components of the pyruvate and 2-oxoglutarate dehydrogenase multienzyme complexes are specifically recognised by their cognate 2-oxo acid decarboxylase (E1p, E1o). A prominent surface loop links the first and second beta-strands in all lipoyl domains, close in space to the lipoyl-lysine beta-turn. This loop was subjected to various modifications by directed mutagenesis of a sub-gene encoding a lipoyl domain of Escherichia coli E2p. Deletion of the loop (four residues) rendered the domain incapable of reductive acetylation by E. coli E1p in the presence of pyruvate, but insertion of a new loop (six residues) corresponding to that in the E2o lipoyl domain partly restored this ability, albeit with a much lower rate. However, the modified domain remained unable to undergo reductive succinylation by E1o in the presence of 2-oxoglutarate. Additional exchange of the two residues on the C-terminal side of the loop (V14A, E15T) had no effect. Insertion of a different four-residue loop also restored a limited ability to undergo reductive acetylation, but still significantly less than that of the wild-type domain. Exchanging the residue on the N-terminal side of the lipoyl-lysine beta-turn in the E2p and E2o domains (G39T), both singly and in conjunction with the loop exchange, had no effect on the ability of the E2p domain to be reductively acetylated but did confer a slight increase in susceptibility to reductive succinylation. All mutant E2p domains, apart from that with the loop deletion (LD), were readily lipoylated in vitro by E. coli lipoate protein ligase A; the E2p LD mutant could be lipoylated only at a significantly lower rate. Likewise, this domain exhibited 1D and 2D NMR spectra characteristic of a partially folded protein, whereas the spectra of mutants with modified loops were similar to those of the wild-type domain. The surface loop is evidently important to the structural integrity of the domain and may help to stabilize the thioester bond linking the acyl group to the reduced lipoyl-lysine swinging arm as part of the catalytic mechanism. Recognition of the lipoyl domain by its partner E1 appears to be a complex process and not attributable to any single determinant on the domain.
J Mol Biol 2000 Jan 14
PMID:Structural determinants of post-translational modification and catalytic specificity for the lipoyl domains of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. 1062 27


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