| 1. |
- Ahnström, Josefin, et al.
(författare)
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Hydrophobic ligand binding properties of the human lipocalin apolipoprotein M
- 2007
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 48:8, s. 1754-1762
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) is a plasma protein associated mainly with HDL. ApoM is suggested to be important for the formation of pre beta-HDL, but its mechanism of action is unknown. Homology modeling has suggested apoM to be a lipocalin. Lipocalins share a structurally conserved beta-barrel, which in many lipocalins bind hydrophobic ligands. The aim of this study was to test the ability of apoM to bind different hydrophobic substances. ApoM was produced both in Escherichia coli and in HEK 293 cells. Characterization of both variants with electrophoretic and immunological methods suggested apoM from E. coli to be correctly folded. Intrinsic tryptophan fluorescence of both apoM variants revealed that retinol, all-trans-retinoic acid, and 9-cis-retinoic acid bound ( dissociation constant 5 2-3 mu M), whereas other tested substances ( e.g., cholesterol, vitamin K, and arachidonic acid) did not. The intrinsic fluorescence of two apoM mutants carrying single tryptophans was quenched by retinol and retinoic acid to the same extent as wild-type apoM, indicating that the environment of both tryptophans was affected by the binding. In conclusion, the binding of retinol and retinoic acid supports the hypothesis that apoM is a lipocalin. The physiological relevance of this binding has yet to be elucidated.
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| 2. |
- Faber, Kirsten, et al.
(författare)
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Characterization of apoM in normal and genetically modified mice
- 2004
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 45:7, s. 1272-1278
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Tidskriftsartikel (refereegranskat)abstract
- A novel human apolipoprotein [apolipoprotein M (apoM)l was recently described and demonstrated to be a lipocalin. We have now examined apoM in wild-type mice and mice with genetically altered lipoprotein metabolism. Liver and kidney showed high mRNA expression, whereas spleen, heart, brain, and testis demonstrated low expression. ApoM gene expression was initiated on embryonic day 10. Western blot analysis of plasma suggested that mouse apoM, like its human counterpart, is secreted with a retained signal peptide, but unlike human apoM it is not glycosylated. Gel filtration of plasma showed apoM to be associated with HDL-sized particles in wild-type and apoA-I-deficient mice and with HDL and LDL-sized particles in LDL receptor-deficient mice, whereas apoM was mainly found in VLDL-sized particles in high-fat, high-cholesterol-fed apoE-deficient mice. The plasma concentration of apoM was similar in wild-type, LDL receptor-deficient, and apoE-deficient mice but was reduced to 33% in apoA-I-deficient compared with wild-type mice (P = 0.007). These data suggest that apoM mainly associates with HDL in normal mice but also with the pathologically increased lipoprotein fraction in genetically modified mice. The substantially decreased apoM levels in apoA-I-deficient mice suggest a connection between apoM and apoA-I metabolism.-Faber, K., O. Axler, B. Dahlback, and L. B. Nielsen. Characterization of apoM in normal and genetically modified mice.
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| 3. |
- Faber, Kirsten, et al.
(författare)
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Megalin is a receptor for apolipoprotein M and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M.
- 2006
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Ingår i: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 20:1, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein ( apo) M is a novel apolipoprotein belonging to the lipocalin protein superfamily, i.e. proteins binding small lipophilic compounds. Like other apolipoproteins, it is expressed in hepatocytes and secreted into plasma where it associates with high-density lipoprotein particles. In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apoM was expressed in Escherichia coli and used in surface plasmon resonance and cell culture studies. The results showed apoM binding to immobilized megalin [ dissociation constant ( K-d) similar to 0.3-1 mu M] and that the apoM was endocytosed by cultured rat yolk sac cells in a megalin-dependent manner. To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis showed that the urinary apoM-containing particles were small and devoid of apoA-1. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine.
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| 4. |
- Snelders, M. P., et al.
(författare)
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Detection of ultra-fast radio bursts from FRB 20121102A
- 2023
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Ingår i: Nature Astronomy. - 2397-3366. ; 7:12, s. 1486-1496
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are extragalactic transient flashes of radio waves with typical durations of milliseconds. FRBs have been shown, however, to present a wide range of timescales: some show sub-microsecond sub-bursts while others last up to a few seconds. Probing FRBs on a range of timescales is crucial for understanding their emission physics, how to detect them effectively and how to maximize their utility as astrophysical probes. FRB 20121102A is the first known repeating FRB source. Here we show that FRB 20121102A produces isolated microsecond-duration bursts with durations less than one-tenth the duration of other currently known FRBs. The polarimetric properties of these microsecond-duration bursts resemble those of the longer-lasting bursts, suggesting a common emission mechanism producing FRBs with durations spanning three orders of magnitude. In detecting and characterizing these microsecond-duration bursts, we show that there exists a population of ultra-fast radio bursts that current wide-field FRB searches are missing due to insufficient time resolution. These results indicate that FRBs occur more frequently and with greater diversity than initially thought. This could also influence our understanding of energy, wait time and burst rate distributions.
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