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  • 351.
    Örtegren Kugelberg, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Yin, Lan
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 14, p. 3381-3392Article in journal (Refereed)
    Abstract [en]

    Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

  • 352.
    Örtegren, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Aboulaich, Nabila
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    A new role for caveolae as metabolic platforms2007In: Trends in endocrinology and metabolism, ISSN 1043-2760, E-ISSN 1879-3061, Vol. 18, no 9, p. 344-349Article in journal (Refereed)
    Abstract [en]

    The plasma membrane of cells functions as a barrier to the environment. Caveolae are minute invaginations of the membrane that selectively carry out the exchange of information and materials with the environment, by functioning as organizers of signal transduction and through endocytosis. Recent findings of uptake of different metabolites and of lipid metabolism occurring in caveolae, point to a new general function of caveolae. As gateways for the uptake of nutrients across the plasma membrane, and as platforms for the metabolic conversion of nutrients, especially in adipocytes, caveolae are now emerging as active centers for many aspects of intermediary metabolism, with implications for our understanding of obesity, diabetes and other metabolic disorders.

  • 353.
    Örtegren, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Margareta
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Blazic, Natascha
    Department of Clinical Neuroscience, Sahlgrenska University Hospital/Mölndal, Göteborg University, Mölndal, Sweden.
    Blomqvist, Maria
    Department of Clinical Neuroscience, Sahlgrenska University Hospital/Mölndal, Göteborg University, Mölndal, Sweden.
    Nyström, Fredrik
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Gustavsson, Johanna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Fredman, Pam
    Department of Clinical Neuroscience, Sahlgrenska University Hospital/Mölndal, Göteborg University, Mölndal, Sweden.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Lipids and glycosphingolipids in caveolae and surrounding plasma membrane of primary rat adipocytes2004In: European Journal of Biochemistry, ISSN 0014-2956, E-ISSN 1432-1033, Vol. 271, no 10, p. 2028-2036Article in journal (Refereed)
    Abstract [en]

    We have made a comprehensive and quantitative analysis of the lipid composition of caveolae from primary rat fat cells and compared the composition of plasma membrane inside and outside caveolae. We isolated caveolae from purified plasma membranes using ultrasonication in carbonate buffer to disrupt the membrane, or extraction with nonionic detergent, followed by density gradient ultracentrifugation. The carbonate-isolated caveolae fraction was further immunopurified using caveolin antibodies. Carbonate-isolated caveolae were enriched in cholesterol and sphingomyelin, and the concentration was three- and twofold higher, respectively, in caveolae compared to the surrounding plasma membrane. The concentration of glycerophospholipids was similar suggesting that glycerophospholipids constitute a constant core throughout the plasma membrane. The composition of detergent-insoluble fractions of the plasma membrane was very variable between preparations, but strongly enriched in sphingomyelin and depleted of glycerophospholipids compared to carbonate-isolated caveolae; indicating that detergent extraction is not a suitable technique for caveolae preparation. An average adipocyte caveola contained about 22 × 103 molecules of cholesterol, 7.5 × 103 of sphingomyelin and 23 × 103 of glycerophospholipid. The glycosphingolipid GD3 was highly enriched in caveolae, whereas GM3, GM1 and GD1a were present inside as well as outside the caveolae membrane. GD1b, GT1b, GM2, GQ1b, sulfatide and lactosylceramide sulfate were not detected in caveolae.

  • 354.
    Örtegren, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Scherer, Philipp
    Albert Einstein College of Medicine, New York, NY, USA.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Localization of adiponectin at the plasma membrane in caveolae of human adipocytesManuscript (preprint) (Other academic)
    Abstract [en]

    The hormone adiponectin is exclusively secreted by adipocytes and it regulates whole body energy homeostasis primarily by affecting liver and muscles. The circulating level of adiponectin inversely correlates with insulin resistance and type 2 diabetes. Little is known about the secretion of adiponectin by the adipocyte, but in caveolin-1 knockout mice the amount of secreted adiponectin is severely reduced. Here we show that in human adipocytes adiponectin was associated with the plasma membrane and to a specific class of high-density-caveolae. Substantial amounts of adiponectin were also found in the microsomal and cytosolic fractions of adipocytes, while very little was associated with mitochondria, nuclei, or the fat. Adiponectin in isolated caveolae was readily degraded by added trypsin, demonstrating that adiponectin was largely bound to the cytosolic face of the caveolae membrane. The findings indicate that caveolae may have a critical role in the secretion of adiponectin by human adipocytes.

  • 355.
    Österström, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Dimberg, Jan
    Fransén, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Expression of cytosolic and group X secretory phospholipase A2 genes in human colorectal adenocarcinomas2002In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 182, no 2, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Gene expression of cytosolic phospholipase A2 (cPLA2) and protein level of secretory PLA2 group X (sPLA2-X) are upregulated in human colorectal cancer and provide cyclooxygenase-2 (COX-2) with arachidonic acid, resulting in increased levels of PGE2. Mutated ras-genes are suggested to be involved in the regulatory pathway of cPLA2 in lung cancer cells. We analysed the gene expression of cPLA2 and sPLA2-X in 42 and 38 primary colorectal tumours, respectively, with and without K-ras mutations. We found an up-regulation of cPLA2 mRNA but the induction in tumour tissues does not correlate with Ras-gene mutations. Moreover, our results cannot consistently reflect an overexpression of sPLA2-X gene in colorectal cancer tissues.

5678 351 - 355 of 355
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