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Titolo:
Influence of glycosylation on the clearance of recombinant human sex hormone-binding globulin from rabbit blood
Autore:
Cousin, P; Dechaud, H; Grenot, C; Lejeune, H; Hammond, GL; Pugeat, M;
Indirizzi:
Hop Antiquaille, Lab Clin Endocrinol, F-69321 Lyon 05, France Hop Antiquaille Lyon France 05 Clin Endocrinol, F-69321 Lyon 05, France Hop Antiquaille, Cent Biochim Lab, F-69321 Lyon, France Hop Antiquaille Lyon France F-69321 nt Biochim Lab, F-69321 Lyon, France Hop Debrousse, INSERM U329, F-69005 Lyon, France Hop Debrousse Lyon France F-69005 sse, INSERM U329, F-69005 Lyon, France Univ Western Ontario, London Reg Canc Ctr, Dept Obstet & Gynecol, London, ON N6A 4L6, Canada Univ Western Ontario London ON Canada N6A 4L6 London, ON N6A 4L6, Canada Univ Western Ontario, London Reg Canc Ctr, Dept Pharmacol & Toxicol, London, ON N6A 4L6, Canada Univ Western Ontario London ON Canada N6A 4L6 London, ON N6A 4L6, Canada
Titolo Testata:
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
fascicolo: 4-6, volume: 70, anno: 1999,
pagine: 115 - 121
SICI:
0960-0760(199909/10)70:4-6<115:IOGOTC>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID SEQUENCE; STEROID-BINDING; PROTEIN SBP; HALF-LIFE; CARBOHYDRATE; PLASMA; TESTOSTERONE; SERUM; EXPRESSION; ESTRADIOL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Pugeat, M Hop Antiquaille, Lab Clin Endocrinol, 1 Rue Antiquaille, F-69321Lyon 05, France Hop Antiquaille 1 Rue Antiquaille Lyon France 05 yon 05, France
Citazione:
P. Cousin et al., "Influence of glycosylation on the clearance of recombinant human sex hormone-binding globulin from rabbit blood", J STEROID B, 70(4-6), 1999, pp. 115-121

Abstract

Human sex hormone-binding globulin (hSHBC) is a plasma glycoprotein that binds sex steroids with high affinity. Variations in hSHBG glycosylation contribute to its electrophoretic microheterogeneity, but the functional significance of different SHBG glycoforms is unknown. Carbohydrates may influence the biological activities and half-lives of glycoproteins and we have examined how oligosaccharides at specific sites influence the plasma clearanceof hSHBG in vivo. To accomplish this, fully-glycosylated hSHBG, or hSHBG mutants lacking specific oligosaccharides chains, were expressed in Chinese hamster ovary (CHO) cells and purified by immunoaffinity chromatography. The purified recombinant proteins were then biotinylated to study their plasma half-lives after intravenous injection into rabbits. When compared to hSHBG isolated from serum, recombinant hSHBG migrates with a slightly larger average molecular size during denaturing polyacrylamide gel electrophoresis. This is due to a greater proportion (33-39% vs. 3%) of more highly branched N-linked oligosaccharides on; the recombinant proteins. When injected into rabbits, the disappearance of recombinant hSHBG showed two exponential components, as previously shown for natural hSHBG in the same animal model. The mean +/- S.E.M. plasma half-lives of recombinant hSHBG (t(1/2)alpha 0.11+/- 0.03 h and t(1/2)beta 18.94 +/- 1.65 h) are shorter than previously measured for natural hSHBG (t(1/2)alpha 3.43 +/- 0.72 h and t(1/2)beta 38.18 /- 7.22 h) and this is likely due to differences in the composition of their N-linked oligosaccharides. An O-linked chain at Thr(7) does not influence the plasma clearance of hSHBG in the presence or absence of N-linked carbohydrates at Asn(351) and Asn(367). However, a 1.5-1.6 fold (p < 0.03) increase in plasma half-life of variants lacking both N-glycosylation sites wasobserved and this is probably due to the fact these variants are not recognized by the asialoglycoprotein receptor-mediated clearance system. Removalof either N-glycosylation consensus site also increased (p < 0.0001) the plasma half-life of hSHBG by 2.3-2.4 fold. Thus, the metabolic clearance of hSHBG appears to be determined by the number of N-linked oligosaccharides rather than their location. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 18:12:01