| 1. |
- Ahnström, Josefin, et al.
(författare)
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HDL Stimulates apoM Secretion.
- 2010
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Ingår i: Protein & Peptide Letters. - 0929-8665. ; Jul 1, s. 1285-1289
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) in human plasma is mainly associated with HDL. A retained signal peptide anchors apoM to the lipoproteins. To investigate the role of the signal peptide in the transfer of apoM from the synthesizing cell to the lipoproteins, wildtype apoM cDNA and the Q(22)A mutant, introducing a signal peptidase cleavage site, were used to stably transfect HEK293 cells, which intrinsically do not express apolipoproteins. When cultured under serum-free conditions, wildtype apoM was, in contrast to Q(22)A, poorly secreted. Addition of serum or purified HDL stimulated secretion of wildtype apoM, which was recovered in the medium incorporated in HDL. The liver cell line HepG2, which synthesizes HDL, was cultured under serum-free conditions and found to secrete apoM as part of an HDL-like particle. In conclusion, due to its retained signal peptide, apoM is poorly secreted unless HDL is either coexpressed or added to the culture medium.
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| 2. |
- 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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| 3. |
- Ahnström, Josefin, et al.
(författare)
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Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies
- 2008
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 49:9, s. 1912-1917
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-beta-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74-1.27) and 0.92 (0.84-1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study.-Ahnstrom, J., O. Axler, M. Jauhiainen, V. Salomaa, A. S. Havulinna, C. Ehnholm, R. Frikke-Schmidt, A. Tybjaerg-Hansen, and B. Dahlback. Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies.
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| 4. |
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| 5. |
- Axler, Olof, et al.
(författare)
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An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol in human plasma
- 2007
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 48:8, s. 1772-1780
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) is a 188 amino acid, 25 kDa protein belonging to the lipocalin protein superfamily. Although predominantly associated with high density lipoprotein, apoM is found in all major lipoprotein classes. To facilitate clinical studies of apoM, we have developed a sandwich ELISA for the measurement of apoM in human plasma. This method has been used to investigate normal apoM variation and to establish reference values for healthy individuals through the measurement of 598 samples from the Nordic Reference Interval Project Bio-bank and Database ( NOBIDA) biobank. For women 18-49 years old, the reference interval for apoM was 0.58-1.18 mu mol/l, whereas for women 501 years and for men, the reference range was 0.61-1.30 mu mol/l. Correlation studies of apoM with 26 common clinical chemical analytes from the NOBIDA database revealed a marked positive correlation with plasma total cholesterol (r = 0.52) and LDL and HDL cholesterol ( r = 0.43 and 0.36, respectively). There was no statistically significant correlation with HDL/total cholesterol ratio or body mass index. In conclusion, a sandwich ELISA for the measurement of apoM in human plasma shows that apoM concentration is strongly correlated to total cholesterol in healthy individuals.
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| 6. |
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| 7. |
- Axler, Olof
(författare)
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APOLIPOPROTEIN M
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Apolipoprotein M (apoM) is composed of 188 amino acids and has an apparent molecular weight of 25 kDa. ApoM belongs to the lipocalin protein superfamily, and is found in all major lipoprotein classes, although the majority of apoM is found in high density lipoprotein, HDL. In apoM, the signal peptide is retained in the mature protein. ApoM with a cleavable signal peptide was constructed. In contrast to wild-type protein, the size of apoM with a cleaved signal peptide corresponded to free, unassociated apoM, strongly indicating that the signal peptide is necessary for the protein´s ability to associate with lipoproteins. To facilitate clinical studies, an ELISA for the measurement of apoM was developed and reference ranges established using samples from the NOBIDA biobank. Correlation studies of apoM with 26 common clinical chemical analytes was performed and a marked positive correlation was observed with plasma total cholesterol (r=0.52) and LDL and HDL cholesterol (r=0.43 and 0.36, respectively). To investigate whether apoM levels predict the risk for coronary disease, apoM was measured in samples from CHD and control subjects drawn from two prospective case-control studies, FINRISK ´92 and the Copenhagen City Heart Study (255 and 1865 individuals in total, respectively). In conditional logistic regression analyses, apoM was not a predictor of CHD events. Plasma apoM was investigated as a possible biomarker for MODY3 disease. Mean serum apoM was 5% lower in carriers of the P291fsinsC mutation of HNF-1a compared to family control subjects. The difference remained statistically significant after exclusion of diabetic individuals but is too small for apoM to be employed as a biomarker for HNF-1a mutation status. In a separate study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetic patients.
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| 8. |
- Axler, Olof, et al.
(författare)
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Apolipoprotein M associates to lipoproteins through its retained signal peptide.
- 2008
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 582:5, s. 826-828
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (apoM) is predominantly associated with HDL. In this study, it was investigated whether apoM's uncleaved signal peptide is necessary for the protein's ability to associate with lipoproteins. ApoM with a cleavable signal peptide, Q22A, was expressed, together with wild-type apoM, in HEK293 cells. On size-exclusion chromatography, the elution profile of wild-type apoM was similar to that of human HDL-associated plasma apoM. In contrast, the size of the Q22A mutant corresponded to free, unassociated apoM. This strongly indicates that the signal peptide is indeed necessary for apoM's ability to associate with lipid.
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| 9. |
- Axler, Olof, et al.
(författare)
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Immunophenotyping of Mature B-Cell Lymphomas
- 2018
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Ingår i: Multiparameter Flow Cytometry in the Diagnosis of Hematologic Malignancies. - : Cambridge University Press. - 9781107503830 - 9781316218549 ; , s. 105-127
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Bokkapitel (refereegranskat)
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| 10. |
- Axler, Olof, et al.
(författare)
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Intermittent Maple Syrup Urine Disease: Two Case Reports
- 2014
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 133:2, s. 458-460
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Tidskriftsartikel (refereegranskat)abstract
- The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain alpha-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or viral gastroenteritis triggers catabolism of muscle protein. Intermittent MSUD should be suspected in cases of common infections with a clinically atypical course, especially in children displaying ataxia or marked drowsiness.
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