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Age-dependent membrane release and degradation of full-length glycosylphosphatidylinositol-anchored proteins in rats.

Mech. Ageing Dev. 190:111307 (2020)
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Open Access Green
Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are associated with the surface of eucaryotic cells only through a covalently coupled carboxy-terminal GPI glycolipid structure which is anchored at the outer leaflet of plasma membranes. This mode of membrane association may be responsible for the recent observations that full-length GPI-APs harbouring the complete GPI anchor are (i) released from isolated rat adipocytes in vitro and (ii) expressed in rat and human serum. The upregulation of the adipocyte release in response to increased cell size and blood glucose/insulin levels of the donor rats and downregulation of the expression in serum of insulin resistant and diabetic rats have been reconciled with enhanced degradation of the full-length GPI-APs released into micelle-like complexes together with (lyso) phospholipids and cholesterol by serum GPI-specific phospholipase D (GPI-PLD).Here by using a sensitive and reliable sensing method for full-length GPI-APs, which relies on surface acoustic waves propagating over microfluidic chips, the upregulation of (i) the release of the full-length GPI-APs CD73, alkaline phosphatase and CD55 from isolated adipocyte plasma membranes monitored in a "lab-on-the-chip" configuration, (ii) their release from isolated rat adipocytes into the incubation medium and (iii) the lipolytic cleavage of their GPI anchors in serum was demonstrated to increase with age (3-16 weeks) and body weight (87 - 477 g) of (healthy) donor rats. In contrast, the amount of full-length GPI-APs in rat serum, as determined by chip-based sensing, turned out to decline with age/body weight. These correlations suggest that age-/weight-induced alterations (in certain biophysical/biochemical characteristics) of plasma membranes are responsible for the release of full-length GPI-APs which becomes counteracted by elevated GPI-PLD activity in serum. Thus, sensitive and specific measurement of these GPI-AP-relevant parameters may be useful for monitoring of age-related cell surface changes, in general, and diseases, in particular.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Glycosylphosphatidylinositol-anchored Proteins ; Lipid Rafts ; Lipolytic Cleavage ; Phospholipase D ; Plasma Membrane Fluidity ; Rat Adipocytes ; Rat Serum; Surface-acoustic-wave; Decay-accelerating Factor; Alkaline-phosphatase; Adipose-tissue; Phospholipase-d; Supported Membranes; Activity Modulation; Plasma-membrane; Cell-growth; Lipid Rafts
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0047-6374
e-ISSN 1872-6216
Quellenangaben Volume: 190, Issue: , Pages: , Article Number: 111307 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-221
G-502296-001
G-502200-001
Grants Helmholtz Alliance "Aging and Metabolic Programming, AMPro
German Research Foundation DFG
Alexander von Humboldt Foundation
Scopus ID 85088091281
Erfassungsdatum 2020-09-23