Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9227
Title: O-glycosylation delays the clearance of human IGF-binding protein-6 from the circulation.
Authors: Marinaro, J A;Casley, David J;Bach, Leon A
Affiliation: Department of Medicine, Austin and Repatriation Medical Centre, University of Melbourne, Heidelberg, Victoria 3084, Australia.
Issue Date: 1-May-2000
Citation: European Journal of Endocrinology / European Federation of Endocrine Societies; 142(5): 512-6
Abstract: The actions of insulin-like growth factors (IGF-I and IGF-II) are modulated by a family of six structurally related, high-affinity binding proteins (IGFBPs 1-6). IGFBP-6, an O-linked glycoprotein, preferentially binds IGF-II and inhibits its actions. The aim of this study was to investigate whether O-glycosylation modulates the pharmacokinetics of IGFBP-6.The pharmacokinetic profiles of (125)I-labelled glycosylated (g) and non-glycosylated (n-g) recombinant human IGFBP-6 were studied following intravenous bolus administration in anaesthetised rats.The redistribution half-life of gIGFBP-6 was 2.3-fold greater than that of n-gIGFBP-6 (14.4+/- 1.2 vs 6.3+/-1.5 min, P=0. 006). The elimination half-life of gIGFBP-6 was 21-fold greater than that of n-gIGFBP-6 (584.2+/-130.2 vs 28.0+/-4.2 min, P=0.019). The effect of O-glycosylation on IGFBP-6 pharmacokinetics was not due to inhibition of intravascular proteolysis. Radioactivity was found in stomach, kidneys, lung, spleen, heart and liver but not brain 4h after injection of g or n-gIGFBP-6.O-glycosylation delays the clearance of IGFBP-6 from the circulation and may therefore contribute to its role as a circulating inhibitor of IGF-II actions.
Internal ID Number: 10802531
URI: http://ahro.austin.org.au/austinjspui/handle/1/9227
URL: http://www.ncbi.nlm.nih.gov/pubmed/10802531
Type: Journal Article
Subjects: Animals
Glycosylation
Half-Life
Humans
Injections, Intravenous
Insulin-Like Growth Factor Binding Protein 6.administration & dosage.metabolism.pharmacokinetics
Iodine Radioisotopes.diagnostic use
Male
Rats
Rats, Sprague-Dawley
Recombinant Proteins.administration & dosage.metabolism.pharmacokinetics
Tissue Distribution
Appears in Collections:Journal articles

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