In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall
Joint Authors
Eltringham-Smith, Louise J.
Gataiance, Sharon
Bhakta, Varsha
Sheffield, William P.
Fox-Robichaud, Alison E.
McCurdy, Teresa R.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-01
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Alpha-1 acid glycoprotein (AGP) is a highly glycosylated plasma protein that exerts vasoprotective effects.
We hypothesized that AGP’s N-linked glycans govern its rate of clearance from the circulation, and followed the disappearance of different forms of radiolabeled human AGP from the plasma of rabbits and mice.
Enzymatic deglycosylation of human plasma-derived AGP (pdAGP) by Peptide: N-Glycosidase F yielded a mixture of differentially deglycosylated forms (PNGase-AGP), while the introduction of five Asn to Gln mutations in recombinant Pichia pastoris-derived AGP (rAGP-N(5)Q) eliminated N-linked glycosylation.
PNGase-AGP was cleared from the rabbit circulation 9-fold, and rAGP-N(5)Q, 46-fold more rapidly than pdAGP, primarily via a renal route.
Pichia pastoris-derived wild-type rAGP differed from pdAGP in expressing mannose-terminated glycans, and, like neuraminidase-treated pdAGP, was more rapidly removed from the rabbit circulation than rAGP-N(5)Q.
Systemic hyaluronidase treatment of mice transiently decreased pdAGP clearance.
AGP administration to mice reduced vascular binding of hyaluronic acid binding protein in the liver microcirculation and increased its plasma levels.
Our results support a critical role of N-linked glycosylation of AGP in regulating its in vivo clearance and an influence of a hyaluronidase-sensitive component of the vessel wall on its transendothelial passage.
American Psychological Association (APA)
McCurdy, Teresa R.& Bhakta, Varsha& Eltringham-Smith, Louise J.& Gataiance, Sharon& Fox-Robichaud, Alison E.& Sheffield, William P.. 2012. In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall. BioMed Research International،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-991624
Modern Language Association (MLA)
McCurdy, Teresa R.…[et al.]. In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall. BioMed Research International No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-991624
American Medical Association (AMA)
McCurdy, Teresa R.& Bhakta, Varsha& Eltringham-Smith, Louise J.& Gataiance, Sharon& Fox-Robichaud, Alison E.& Sheffield, William P.. In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall. BioMed Research International. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-991624
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-991624