Disease relevance of Saa2

• Inbred strains of mice provide a model for studies of the pathogenesis of amyloid A (AA) amyloidosis [1].
• Additionally, we identified the IL-6-gp130-STAT3-dependent proteins KC and SAA2 as new candidates for therapeutic targets in liver diseases [2].
• In contrast, C5a protected terminally differentiated human neuroblastoma cells from toxicity mediated by the amyloid A beta peptide [3].
• Three human DNA fragments hybridizing to a mouse cDNA plasmid for the acute phase protein amyloid A have been isolated from the human lambda Charon 4A phage library [4].
• Increased T-cell responsiveness was associated with an increased acute-phase response and amyloid A deposition in the glomerulus of these mice [5].

High impact information on Saa2

• Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses [6].
• Amyloid A fibrils in spleen homogenates were denatured by formic acid and AA protein was quantified by ELISA using anti-mouse apoSAA antibodies [1].
• Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of 123I-labeled serum amyloid P component (SAP) [7].
• Gene conversion, sometimes also called micro gene conversion or gene conversion-like events, has been proposed to act on a number of genes in higher eukaryotes, such as gamma-globin, beta-tubulin, major urinary protein, and amyloid A genes [8].
• Its synthesis is tissue-specific in that amyloid A mRNA was not detected in the kidney, an important site of amyloid fibril accumulation [9].

Chemical compound and disease context of Saa2

• The heparin/heparan sulfate-binding site on apo-serum amyloid A. Implications for the therapeutic intervention of amyloidosis [10].
• Inhibition of amyloid A amyloidogenesis in vivo and in tissue culture by 4-deoxy analogues of peracetylated 2-acetamido-2-deoxy-alpha- and beta-d-glucose: implications for the treatment of various amyloidoses [11].

Biological context of Saa2

• Kinetics of SAA protein distribution and gene expression after acute phase stimulation by casein or lipopolysaccharide were examined using immunocytochemistry for protein and RNA blot and in situ hybridization with probes for SAA1 and SAA2 mRNA [12].
• Amino acid sequence studies of the amino terminal 25 residues of amyloid A (AA) protein and the serum precursor (SAA) induced with casein or LPS indicate differences in the sequence at position 6 and significant heterogeneity at several other positions in SAA [13].
• Immunolocalization of lipid peroxidation/advanced glycation end products in amyloid A amyloidosis [14].
• These proteins undergo a post-translational modification to yield amyloid A, molecules that share with PrP the ability to polymerize into birefringent filaments [15].
• Saa1 and Saa2 in the BALB/c strain are 72% identical over the first 500 bp upstream of their transcription start sites and to date have been considered to be coordinately regulated [16].

Anatomical context of Saa2

• Two additional members of the murine Saa gene family, Saa1 and Saa2, were also detected in irradiated bone marrow [17].
• Extrahepatic SAA1 and SAA2 mRNA were induced by lipopolysaccharide in kidney proximal and distal convoluted tubule epithelia, and SAA1 mRNA was induced in epithelial lining the mucosa of the ileum and large intestine, indicating that there may be more than one function for the apoSAA gene family related to site of and stimulus for expression [12].
• Regulation of amyloid A gene expression in cultured cells [18].
• Murine tissue macrophages synthesize and secrete amyloid proteins different to amyloid A (AA) [19].
• Generation of amyloid A protein by the cell lines from amyloid-susceptible and -resistant mice [20].

Associations of Saa2 with chemical compounds

• In experimental chronic inflammation, daily injection of silver nitrate (AgNO3) resulted in the deposition of 667 +/- 68 ng of amyloid A protein (AA)/mg of spleen after 25 days [21].
• AEF can be solubilized in 4 M glycerol, is not the amyloid A protein, and is not likely to be the serum amyloid P component [22].
• PGE1 lowered splenic deposition of amyloid A protein (AA) (p = 0.035) [23].
• ME3738 treatment in male mice increased gene expression of alpha1-acid glycoprotein subtypes and serum amyloid A 2 genes, and plasma concentration of serum amyloid A. Treatment with alpha1-acid glycoprotein at 5 mg/animal or serum amyloid A at 0.03 and 0.1 mg/animal prior to concanavalin A administration reduced multifocal necrosis in the liver [24].
• Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months [25].

Regulatory relationships of Saa2

• Amyloid A protein amyloidosis induced in apolipoprotein-E-deficient mice [26].

Other interactions of Saa2

• Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice [27].
• Cytokines, haptoglobin, adiponectin and amyloid A levels were analyzed with ELISA [28].
• Treatment with interferon-gamma was found to restore decreased Ia expression in animals given AEF+AgNO3 but did not prevent amyloid A fibril deposition [29].
• It has been proposed that impaired degradation is the cause of amyloid A (AA) formation in reactive amyloidosis (Ham et al., Scand J Immunol 1997; 45: 354-60) [20].
• Activation of STAT-3 and three STAT-3 responsive genes, Socs3, Cd14, and serum amyloid A2 were also blocked [30].

Analytical, diagnostic and therapeutic context of Saa2

• The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy [27].
• Amyloid fibrils were isolated from spleens and the subunit amyloid A (AA) protein purified by gel filtration on a column of Sepharose CL6B [31].
• Amyloidosis was quantitated by radioimmunoassay for splenic amyloid A (AA) protein [32].
• The neurotoxicity of amyloid A beta peptides has been linked to peroxide generation in cell cultures by an unknown mechanism [33].
• Immunohistochemistry, the standard method for diagnosing amyloid A (AA) amyloidosis, is limited in animals because it requires a large array of animal-specific anti-AA antibodies, not commercially available [34].

References