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Uptake sites and half-life of plasma bikunin.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
(English)Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-90612OAI: oai:DiVA.org:uu-90612DiVA: diva2:163031
Available from: 2003-05-13 Created: 2003-05-13 Last updated: 2011-06-28Bibliographically approved
In thesis
1. Proteins of the Inter-α-inhibitor Family: Biosynthesis, Plasma Clearance and Interaction with Extracellular Matrix Components
Open this publication in new window or tab >>Proteins of the Inter-α-inhibitor Family: Biosynthesis, Plasma Clearance and Interaction with Extracellular Matrix Components
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bikunin, a chondroitin sulfate-containing protein of 25 kDa, has protease inhibitory activity and occurs in the plasma in free and complexed form. In inter-α-inhibitor (IαI) and pre-a-inhibitor (PαI) it is covalently linked through its chondroitin sulfate (CS) chain to two or one other polypeptide of about 80 kDa – heavy chains 1 and 2 (H1, H2) and heavy chain 3 (H3) – respectively. Bikunin and the heavy chains are synthesized as precursors, which are proteolytically cleaved and assembled into IαI and PαI in the secretory pathway. The C-terminal extension (CTX) of the heavy chains seems to mediate its own cleavage and theassembly of the complexes. The heavy chains of the IαI family become transferred to hyaluronan during ovulation and inflammation.

In this thesis, the biosynthesis of PαI, the plasma clearance of bikunin and the binding of IαI to collagen were studied. We found that in H3, a short segment on the N-terminal side of the CTX cleavage site is required for cleavage. Furthermore, the H3 could become linked to free CS chains primed by a xyloside, showing that the bikunin protein core is not needed for coupling. We also identified His649 as a residue essential for coupling, but not for cleavage.

Bikunin labelled with a residualizing agent, 125I-tyramine cellobiose, was injected into mice to identify tissues involved in its uptake. Half of the radioactivity was recovered in the kidneys, 10% in the liver, and the rest distributed in other tissues. We determined the half-life of bikunin in rat plasma using two independent methods: injection of 125I-bikunin, or hepatectomy followed by assessing the rate of disappearance of endogenous bikunin. Both methods yielded half-time values of 5-7 minutes. Removal of the CS chain did not affect the clearance rate of bikunin.

IαI and its heavy chains were found to bind to collagen with dissociation constants greater than 2 μM and 0.4-0.6 μM, respectively and this binding was independent of divalent metal ions. We suggest that the interaction of IαI with collagen may play a modulatory role in cell migration or in remodelling of the extracellular matrix.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 59 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1274
Biochemistry, bikunin, inter-α-inhibitor, pre-α-inhibitor, intracellular processing, plasma clearance, extracellular matrix, binding, collagen, Biokemi
National Category
Biochemistry and Molecular Biology
Research subject
Medical Biochemistry
urn:nbn:se:uu:diva-3495 (URN)91-554-5672-3 (ISBN)
Public defence
2003-06-03, C10:305, Biomedical Center, Uppsala, 09:15
Available from: 2003-05-13 Created: 2003-05-13Bibliographically approved

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