Serum amyloid

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

CRP , complement , PLA2 , serum amyloid A , fibrinogen , c -acid glycoprotein , IL-1Ra , ceruloplasmin , ai-antichymotrypsin , LBP albumin , haptoglobin , IGF-1 , transferrin , u2-HS glycoprotein ... 

Heegard, N. H. H. and Robey, R A., Use of capillary zone electrophoresis to evaluate the binding of anionic carbohydrates to synthetic peptides derived from human serum amyloid P component, Anal. Chem., 64, 2479, 1992. 

CAIA, collagen Ab-induced arthritis CIA, collagen-induced arthritis SAP, serum amyloid P-component. 

Immunoglobulin light chain Immunoglobulin heavy chain Apo-serum amyloid A protein... 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

Yamada T, Kluve Beckerman B, Liepnieks JJ, Benson MD. Fibril formation from recombinant human serum amyloid A. Biochim Biophys Acta 1994 1226 323-329. 

Serum amyloids Coagulation factors Tumor necrosis factor Erythrocyte proteins Apolipoproteins... 

HSAB and sulfo-HSAB have been used to investigate serum amyloid A (Cai et al., 2007), the functional role of C-terminal sequence elements in the transporter associated with antigen processing (Ehses et al., 2005), and the kinetics of intermolecular interactions during cytochrome C protein folding (Nishida et al., 2004). 

AP and tau, 6-2 microglobulin Immunoglobulin light chain Serum amyloid A (SAA) Transthyretin (TTR) Apolipoprotein A-l Cystatin A Gelsolin... 

Concerning the nature and structure of such amyloid peptide or protein channels, oligomers with annular morphologies have in fact been observed by EM for a-synuclein (Lashuel et al., 2002) and equine lysozyme (Malisauskas et al., 2003) even in the absence of any lipids or membranes. Channel-like structures have also been reconstituted in liposomes and observed by SFM for A/ i 4o, A/ j 42, human amylin, a-synuclein, ABri, ADan, and serum amyloid A (Fig. 5A Lin et al., 2001 Quist et al., 2005). Doughnut-shaped structures with a diameter of 10-12 nm and a central hole size of 1-2 nm (Fig. 5B) were imaged on top of lipid membranes (Quist et al., 2005). However, the radius of curvature of the SFM tips meant that it is not possible to say whether the pores were really traversing the lipid bilayer. 

Pepys, M.B., Herbert, J., Hutchinson, W.L., et al. (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature, 417, 254-259. 

NHH Heegaard, HD Mortensen, P Roepstorff. Demonstration of a heparinbinding site in serum amyloid P component using affinity capillary electrophoresis as an adjunct technique. J Chromatogr A 717 83—90, 1995. 

NHH Heegaard, PMH Heegaard, P Roepstorff, FA Robey. Ligand-binding sites in human serum amyloid P component. Eur J Biochem 239 850—856, 1996. 

Amyloid pi 42-peptide (Apj 42). Serum amyloid A is an acute-phase protein. Using a monoclonal ELISA, it can be established in the serum and CSF and its intrathecal synthesis seems very common in AIDS patients and in some other inflammatory processes (S5). 

Hawkins. P. el ah F.valuation of Systemic Amyloidosis by Scinngraphy with 1231-Labeled Serum Amyloid P Component. iV. /.lie. / Met .. SDH (August 23. 199tii. 

Kisilevsky R. Serum amyloid A (SAA), a protein without a function Some suggestions with reference to cholesterol metabolism. Med Hypotheses 1991 35 337-341. 

Lindhorst E, Young D, Bagshaw W, Hyland M, Kisilevsky R. Acute inflammation, acute phase serum amyloid A and cholesterol metabolism in the mouse. Biochim Biophys Acta 1997 1339 143-154. 

Steinmetz A, Hocke G, Saile R, Puchois P, Fruchart JC. Influence of serum amyloid A on cholesterol esterification in human plasma. Biochim Biophys Acta 1989 1006 173-178. 

Tam SP, Flexman A, Hulme J, Kisilevsky R. Promoting export of macrophage cholesterol The physiological role of a major acute-phase protein, serum amyloid. A J Lipid Res 2002 43 1410-1420. 

Several prospective studies have shown that markers of inflammation, such as sensitive C-reactive protein and serum amyloid A (S-AA), are predictors of increased risk for myocardial infarction, stroke, or peripheral vascular disease (53-56). 

Jousilahti R et al. Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status. J Epidemiol Community Health 2003 57(9) 730-733. 

Fyfe Al, et al. Association between serum amyloid A proteins and coronary artery disease evidence from two distinct arteriosclerotic processes. Circulation 1997 96(9) 2914-2919. 

Many mediators of inflammation have been identified— cytokines IL-6, tumor necrosis factor alpha cell adhesion molecules intracellular adhesion molecule-1 (ICAM-I), P-selectin and acute phase reactants CR.R fibrinogen, serum amyloid A, and soluble CD40 (Fig. I) (3). Myeloperoxidase is an enzyme secreted from monocytes, neutrophils, and macrophages. A single measurement taken from patient with chest pain in the emergency department predicted the early risk of myocardial infarction and the risk of major cardiac of ends in the next 30 days to six months (15). 

B19. Bausserman, L. L., Herbert, P. N., Rodger, R., and Nicolosi, R. J., Rapid clearance of serum amyloid A from high-density lipoproteins. Biochim. Biophys. Acta 792, 186-191 (1984). 

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