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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the allele and genotype frequencies in Italians of eight unlinked commonly utilized polymorphic loci: HUMTH01, HUMFES/FPS, HLA-DQA1, LDLR, GYPA, HBGG, D7S8 and GC. Genomic DNA from at least 100 individuals was amplified by PCR and typed after electrophoresis (HUMTH01, HUMFES/FPS), or reverse dot-blot (HLA-DQA1 and the other five loci). The allelic frequencies determined were compared with available population data. These results are useful for population and individual identification studies.
Mol Cell Probes 1995 Jun
PMID:Allele and genotype frequencies of eight DNA polymorphisms in the Italian population. 747 11

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.
Mol Cell 2001 Jan
PMID:A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. 1117 21

We have previously shown that infection with the C. pneumoniae AR39 strain once monthly for 9 consecutive months significantly exacerbated atherosclerosis in mice with LDL receptor deficiency (LDLR-/-) in the presence of a high cholesterol diet. To further optimize the LDLR-/- mouse model for studying the mechanisms of C. pneumoniae atherogenesis, we have tested a different infection protocol with intranasal inoculation twice monthly for 6 consecutive months in the present study. We found that C. pneumoniae infection for 6 months was sufficient to produce a 130%, significantly greater exacerbation of aortic atherosclerosis in LDLR-/- mice in the presence of a high cholesterol diet. Mice receiving a high cholesterol diet alone displayed a lesion area index of 18.2 +/- 6.1 (S.D.) while mice treated with both the high cholesterol diet and C. pneumoniae infection had a lesion area index of 41.8 +/- 15.2 (S.D.). However, the chlamydial infection did not significantly alter the mouse serum total cholesterol or the LDL levels induced by the high cholesterol diet. This study not only confirms our previous findings that C. pneumoniae infection can exacerbate aortic atherosclerosis lesion in the LDLR-/- mice, but also further optimizes the LDLR-/- mouse model for future mechanism studies.
Mol Cell Biochem 2000 Dec
PMID:Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR-/- mouse model within six months. 1120 47

Lipophorin (Lp) functions as a yolk protein precursor in the mosquito Aedes aegypti and it is internalized via receptor-mediated endocytosis (Insect Biochem. Mol. Biol., 30 (2000) 1161). We cloned and molecularly characterized a putative mosquito ovarian lipophorin receptor (AaLpRov) cDNA. The cDNA has a length of 3468 bp coding for a 1156-residue protein with a predicted molecular mass of 128.9 kDa. The deduced amino acid sequence of the cDNA revealed that it encodes a protein homolog of the LDL receptor superfamily, and that it harbors eight cysteine-rich ligand binding repeats at the N-terminus like vertebrate VLDL receptors. The deduced amino acid sequence of this mosquito ovarian receptor is most similar to that of the locust lipophorin receptor (LmLpR) (64.3%), and is only distantly related to the mosquito vitellogenin receptor (VgR) (18.3%), another ovarian LDLR homolog with a different ligand. The AaLpRov cDNA was expressed in a TnT Coupled Reticulocyte Lysate system, and co-immunoprecipitation experiments confirmed that the receptor protein specifically binds Lp. Developmental expression profiles clearly showed that AaLpRov transcripts are present in the vitellogenic ovary, with peak expression at 24-36 h post blood meal. In situ hybridization indicated that AaLpRov transcripts are present only in female germ line cells. Distance-based phylogenetic analyses suggest that the insect LpR and vertebrate LDL/VLDL receptor lineages separated after divergence from the insect VgR lineage.
Insect Biochem Mol Biol 2001 Jun 22
PMID:Molecular characterization of the VLDL receptor homolog mediating binding of lipophorin in oocyte of the mosquito Aedes aegypti. 1137 10

Despite similar functions, the yolk proteins of the higher dipteran flies and the vitellogenins found in other insects are unrelated at the sequence level and have evolved from different genes. Both are selectively endocytosed into the ovary via receptors belonging to the LDLR receptor subfamily. We cloned the Drosophila yp1 gene into an E. coli expression vector and showed that the yolk protein produced by E. coli is taken up into ovaries of both Drosophila melanogaster and the malaria mosquito Anopheles gambiae, which normally uses vitellogenin.
Insect Mol Biol 2002 Oct
PMID:Drosophila yolk protein produced in E. coli is accumulated by mosquito ovaries. 1223 May 47

We have developed and clinically tested a rapid and largely automated procedure to detect mutations in the coding region of a gene of interest. Our method relies on the automated sequencing of the complete cDNA, followed by an advanced mutation search-and-verification routine using an integrated set of computer analysis tools. We have applied our automated procedure to the diagnosis of familial hypercholesterolemia (FH) in 52 unrelated FH families, by sequencing the whole cDNA coding region of the LDLR gene. Here we report the procedures and performance of our method in the identification of the most common types of LDLR mutations: short deletions or insertions and point mutations. Our method can provide a standard procedure for the 'overnight' unequivocal identification of mutations in those genetic diseases where several different mutations, none clearly prominent, may affect a given gene.
Mol Cell Probes 2003 Feb
PMID:A rapid method for detecting mutations of the human LDL receptor gene by complete cDNA sequencing. 1262 89

Macrophage scavenger receptors (MSR) promote atherosclerotic lesion formation, and modulation of MSR activity has been shown to influence atherosclerosis. Soluble receptors are effective in inhibiting receptor-mediated functions in various diseases. We have generated a secreted macrophage scavenger receptor (sMSR) that consists of the bovine growth hormone signal sequence and the human MSR A I extracellular domains. sMSR reduces degradation of atherogenic modified low-density lipoproteins and monocyte/macrophage adhesion on endothelial cells in vitro. To test long-term effects of sMSR, atherosclerosis-susceptible LDLR knockout mice were transduced via the tail vein with an adeno-associated virus (AAV) expressing sMSR or control enhanced green fluorescent protein (EGFP), and a Western-type diet was started. Gene transfer caused a temporary elevation in alkaline phosphatase and aspartate amino transferase values without a change in C-reactive protein. sMSR protein was detected in the plasma of the transduced mice by a specific ELISA 6 months after the gene transfer. AAV-mediated sMSR gene transfer reduced atherosclerotic lesion area in the aorta by 21% (P < 0.05) compared to EGFP-transduced control mice. Even though eradication of established disease was not possible, atherosclerotic lesion formation could be modified using AAV-mediated gene transfer of the decoy sMSR.
Mol Ther 2003 Dec
PMID:Adeno-associated virus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor reduces atherosclerotic lesion formation in LDL receptor knockout mice. 1466 92

Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model' showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.
Hum Mol Genet 2004 May 15
PMID:Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol. 1504 81

We have previously shown that infection with Chlamydia pneumoniae can significantly exacerbate atherosclerotic lesions in LDLR-/- mice concurrently fed a high cholesterol diet in 6 or 9 months. We now report that a period of 4 month was sufficient for demonstrating the C. pneumoniae atherogenicity. However, heat inactivation of C. pneumoniae organisms completely abolished the ability of C. pneumoniae to exacerbate the atherosclerotic lesions, suggesting that viable organism infection may be required for the C. pneumoniae atherogenicity.
Mol Cell Biochem 2004 May
PMID:Heat-inactivated C. pneumoniae organisms are not atherogenic. 1522 96

Serine proteases play vital roles in several biological processes such as development and immunity. We have characterized Graal, a large multi-domain serine protease from Drosophila. Graal is spliced in at least three transcripts that are present throughout development. The domains found in Graal proteins are: chitin-binding domains (CBD), scavenger receptor cysteine-rich (SRCR) domains, low density lipoprotein receptor cysteine-rich (LDLR-CR) domains, histidine and proline-rich domains, a NGGYQPP-repeat domain and a serine protease domain. The last 2370 nucleotides of these RNAs are identical and encode a His-rich domain, two SRCR domains, two LDLR-CR domains and a protease domain. The transcription of graal is upregulated after fungal or bacterial infection. Analysis of the Iso1 (y;cn,sp,bw) strain shows that graal transcription is impaired in this fly line due to the insertion of a retrotransposon in the sixth exon. However, no phenotype could be observed consecutive to the absence of graal full length transcripts, particularly in the context of an immune challenge.
Insect Biochem Mol Biol 2004 Oct
PMID:graal: a Drosophila gene coding for several mosaic serine proteases. 1547 97


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