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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Biemer-daub, G. Wied, S. Jung, C. Müller, G. |
| Description | Author Affiliation: Müller G ( Sanofi-Aventis Pharma, R & D, Therapeutic Department Metabolism, Frankfurt am Main, Germany. Guenter.Mueller@sanofi-aventis.com) |
| Abstract | BACKGROUND AND PURPOSE: Adipocytes release membrane vesicles called adiposomes, which harbor the glycosylphosphatidylinositol-anchored proteins (GPI proteins), Gce1 and CD73, after induction with palmitate, H(2)O(2) and the sulphonylurea drug glimepiride. The role of lipid droplets (LD) in trafficking of GPI proteins from detergent-insoluble, glycolipid-enriched, plasma membrane microdomains (DIGs) to adiposomes in rat adipocytes was studied. EXPERIMENTAL APPROACH: Redistribution of Gce1 and CD73 was followed by pulse-chase and long-term labelling, western blot analysis and activity determinations with subcellular fractions and cell-free systems exposed to palmitate, H(2)O(2) and glimepiride. KEY RESULTS: In response to these signals, Gce1 and CD73 disappeared from DIGs, then transiently appeared in LD and finally were released into adiposomes from small, and, more efficiently, large adipocytes. From DIGs to LD, Gce1 and CD73 were accompanied by cholesterol. Cholesterol depletion from DIGs or LD caused accumulation at DIGs or accelerated loss from LD and release into adiposomes, respectively, of the GPI proteins. Blockade of translocation of Gce1, CD73, caveolin-1 and perilipin-A from DIGs to LD blocked LD biogenesis and long term-accumulation of LD interfered with induced release of the GPI proteins into adiposomes. GPI protein release was up-regulated upon long term-depletion of LD. Adiposomes were released by a DIGs-based cell-free system, but only in presence of LD. CONCLUSIONS: GPI proteins are translocated from DIGs to LD prior to their release into adiposomes, which is regulated by cholesterol, LD content and LD biogenesis. This detour may serve to transfer information about the LD content and to control lipolysis/esterification between large and small adipocytes via GPI protein-harbouring adiposomes. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 158 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2009-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | 5'-Nucleotidase Metabolism Adipocytes Glycosylphosphatidylinositols Membrane Microdomains Phosphoric Diester Hydrolases Ultrastructure Animals Carrier Proteins Caveolin 1 Cells, Cultured Cholesterol Endoplasmic Reticulum Endosomes Exosomes Hydrogen Peroxide Pharmacology Palmitates Phosphoproteins Protein Transport Rats, Sprague-Dawley Sulfonylurea Compounds |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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