Heparan sulfate/heparin-HDL interaction dissociates serum amyloid A (SAA) from HDL-SAA complex leading to SAA aggregation
2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 30, 25669-25677 p.Article in journal (Refereed) Published
Inflammation-related (AA) amyloidosis is a severe clinical disorder characterized by the systemic deposition of the acute-phase reactant serum amyloid A (SAA). SAA is normally associated with the high-density lipoprotein (HDL) fraction in plasma, but under yet unclear circumstances, the apolipoprotein is converted into amyloid fibrils. AA amyloid and heparan sulfate (HS) display an intimate relationship in situ, suggesting a role for HS in the pathogenic process. This study reports that HS dissociates SAA from HDLs isolated from inflamed mouse plasma. Application of surface plasmon resonance spectroscopy and molecular modeling suggests that HS simultaneously binds to two apolipoproteins of HDL, SAA and ApoA-I, and thereby induce SAA dissociation. The activity requires a minimum chain length of 12-14 sugar units, proposing an explanation to previous findings that short HS fragments preclude AA amyloidosis. The results address the initial events in the pathogenesis of AA amyloidosis.
Place, publisher, year, edition, pages
2012. Vol. 287, no 30, 25669-25677 p.
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-168314DOI: 10.1074/jbc.M112.363895ISI: 000306651700074OAI: oai:DiVA.org:uu-168314DiVA: diva2:492870
Manuscript title: Heparan sulfate/heparin-HDL interaction dissociates serum amyloid A (SAA) from HDL-SAA complex leading to SAA aggregation2012-02-082012-02-082013-02-12Bibliographically approved