Heparan Sulfate Dissociates Serum Amyloid A (SAA) from Acute-phase High-density Lipoprotein, Promoting SAA Aggregation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Jun 2

PMID 22654109

Citations 19

Authors

Fredrik Noborn

John B Ancsin

Wimal Ubhayasekera

Robert Kisilevsky

Jin-Ping Li

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Cevc G . Membrane electrostatics. Biochim Biophys Acta. 1990; 1031(3):311-82. DOI: 10.1016/0304-4157(90)90015-5. View

Jha S, Patil S, Gibson J, Nelson C, Alder N, Alexandrescu A . Mechanism of amylin fibrillization enhancement by heparin. J Biol Chem. 2011; 286(26):22894-904. PMC: 3123057. DOI: 10.1074/jbc.M110.215814. View

Morrow J, Stearman R, Peltzman C, Potter D . Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci U S A. 1981; 78(8):4718-22. PMC: 320234. DOI: 10.1073/pnas.78.8.4718. View

Gabay C, Kushner I . Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999; 340(6):448-54. DOI: 10.1056/NEJM199902113400607. View

Wall J, Richey T, Stuckey A, Donnell R, Macy S, Martin E . In vivo molecular imaging of peripheral amyloidosis using heparin-binding peptides. Proc Natl Acad Sci U S A. 2011; 108(34):E586-94. PMC: 3161606. DOI: 10.1073/pnas.1103247108. View

Karplus K, Karchin R, Barrett C, Tu S, Cline M, Diekhans M . What is the value added by human intervention in protein structure prediction?. Proteins. 2002; Suppl 5:86-91. DOI: 10.1002/prot.10021. View

Elimova E, Kisilevsky R, Szarek W, Ancsin J . Amyloidogenesis recapitulated in cell culture: a peptide inhibitor provides direct evidence for the role of heparan sulfate and suggests a new treatment strategy. FASEB J. 2004; 18(14):1749-51. DOI: 10.1096/fj.03-1436fje. View

Tam S, Kisilevsky R, Ancsin J . Acute-phase-HDL remodeling by heparan sulfate generates a novel lipoprotein with exceptional cholesterol efflux activity from macrophages. PLoS One. 2008; 3(12):e3867. PMC: 2588651. DOI: 10.1371/journal.pone.0003867. View

Krimbou L, Tremblay M, Davignon J, Cohn J . Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre-beta1-LpE, pre-beta2-LpE, and alpha-LpE. J Lipid Res. 1997; 38(1):35-48. View

10.

Lundmark K, Westermark G, Olsen A, Westermark P . Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism. Proc Natl Acad Sci U S A. 2005; 102(17):6098-102. PMC: 1087940. DOI: 10.1073/pnas.0501814102. View

11.

Gestwicki J, Hsieh H, Pitner J . Using receptor conformational change to detect low molecular weight analytes by surface plasmon resonance. Anal Chem. 2002; 73(23):5732-7. DOI: 10.1021/ac0105888. View

12.

Lindahl U, Li J . Interactions between heparan sulfate and proteins-design and functional implications. Int Rev Cell Mol Biol. 2009; 276:105-59. DOI: 10.1016/S1937-6448(09)76003-4. View

13.

Gillmore J, Lovat L, Persey M, Pepys M, Hawkins P . Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet. 2001; 358(9275):24-9. DOI: 10.1016/S0140-6736(00)05252-1. View

14.

Mulgrew-Nesbitt A, Diraviyam K, Wang J, Singh S, Murray P, Li Z . The role of electrostatics in protein-membrane interactions. Biochim Biophys Acta. 2006; 1761(8):812-26. DOI: 10.1016/j.bbalip.2006.07.002. View

15.

Danielsson A, Raub E, Lindahl U, BJORK I . Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa. J Biol Chem. 1986; 261(33):15467-73. View

16.

Ancsin J, Kisilevsky R . The heparin/heparan sulfate-binding site on apo-serum amyloid A. Implications for the therapeutic intervention of amyloidosis. J Biol Chem. 1999; 274(11):7172-81. DOI: 10.1074/jbc.274.11.7172. View

17.

Westermark G, Westermark P . Serum amyloid A and protein AA: molecular mechanisms of a transmissible amyloidosis. FEBS Lett. 2009; 583(16):2685-90. DOI: 10.1016/j.febslet.2009.04.026. View

18.

Cardin A, WEINTRAUB H . Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis. 1989; 9(1):21-32. DOI: 10.1161/01.atv.9.1.21. View

19.

Brux C, Ben-David A, Shallom-Shezifi D, Leon M, Niefind K, Shoham G . The structure of an inverting GH43 beta-xylosidase from Geobacillus stearothermophilus with its substrate reveals the role of the three catalytic residues. J Mol Biol. 2006; 359(1):97-109. DOI: 10.1016/j.jmb.2006.03.005. View

20.

Staatz W, Toyoda H, Chhor K, Selleck S . Analysis of proteoglycans and glycosaminoglycans from Drosophila. Methods Mol Biol. 2001; 171:41-52. DOI: 10.1385/1-59259-209-0:041. View