Amyloid A, serum

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 ... 

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. 

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. 

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). 

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). 

P5. Parks, J. S., and Rudel, L. L., Metabolism of the serum amyloid A proteins (SAA) in high-density lipoproteins and chylomicrons of nonhuman primates (vervet monkey). Am. /. Pathol. 112, 243-249 (1983). 

MS-based mass profiling combined with multivariate analysis identified platelet factor 4, a chemokine with prothrombolytic and antiangiogenic activities, as a diagnostically predictive protein in depleted serum of prostate cancer patients [99]. SELDI-TOF-MS was applied to the discovery of serum markers of bone metastasis in prostate cancer. Unique isoforms of serum amyloid A were identified in these patients. Machine-learning algorithms were used to identify these patients with a sensitivity and specificity of 89% [100],... 

Le L, Chi K, Tyldesley S, Flibotte S, Diamond DL, Kuzyk MA, et al. Dentification of serum amyloid A as a biomarker to distinguish prostate cancer patients with bone lesions. Clin Chem 2005 51(4) 695-707. 

AA amyloidosis0 Fragments of serum amyloid A protein 76-104d All-a, unknown fold... 

Benigni, F., Fantuzzi, G., Sacco, S., Sironi, M., Pozzi, P., Dinarello, C. A., Sipe, J. D., Poli, V., Cappelletti, M., and Paonessa, G. et al. (1996). Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1. Blood 87, 1851-1854. 

Tuberculosis and Rheumatoid arthritis Serum amyloid A Systemic... 

The amyloid is of the secondary type, amyloid A protein. Serum amyloid A, an acute phase reactant produced by hepatocytes, circulates complexes to high density lipoprotein and is cleaved into smaller fragments which subsequently polymerize into the alpha pleated sheet configuration of amyloid [57, 68]. The renal amyloid is heavily distributed in the tubular... 

Fig. 16. Two amphipathic helical segements of serum amyloid A. (A) Residues 1—24 (B) residues 53-73.

Serum amyloid A (SAA), an acute-phase protein, is not a major protein component of normal HDL. However, during an acute-phase response, the concentration of this protein increases and it specifically associates with HDL (Olphin and Price, 1988). Therefore, it is necessary to understand the properties of this protein from the point of view of the nature of the amphipathic helix present in this protein. SAA associates with... 

Several of the proteins in Table 20-3 are acute phase reactants (APR) with the concentrations of tti-antitrypsin (AAT), aj-acid glycoprotein (AAG), haptoglobin (Hp), ceruloplasmin, C4, C3, procalcitonin (PCT), and serum amyloid A (SAA) increasing in most forms of inflammation these are called positive APR. Others, such as transthyretin... 

IL-6 acts on the pituitary to induce adrenocorticotropic hormone (ACTH) release and directly on the adrenal glands to produce glucocorticoids. It is known that different cytoldnes that share gpl30 as a receptor subunit induce serum amyloid A, and potentiate the induction of IL-6 and the activation of the hypothalamic-pituitary-adrenal axis by IL-1. In particular, LIF, OSM, IL-11, and cardiotrophin-1 potentiate the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, the potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. Thus either endogenous IL-6 does not mediate IL-l-induced corticosterone increase, or its role may be fulfilled by other cytokines. This is very important in the understanding of the activation of the hypothalamic-pituitary-adrenal axis and that potentiation of acute phase protein synthesis may represent an important feedback regulatory mechanism of inflammation. ... 

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