Disease relevance of SAA2

• SAA2 had no effect on renal amyloidosis [1].
• SAA2 promoter-driven luciferase reporter gene constructs carrying the SAA2 5'-UTR and/or 3'-UTR were transiently transfected into the HepG2 human hepatoma cell line [2].
• To understand the mechanisms by which large increases in serum amyloid A (SAA) occur during the acute phase response, human hepatoma cells were transfected with SAA2 gene reporter plasmids and stimulated with combinations of cytokines [3].
• The SAA2-tat/HIV-sTNFR:Ig construct retained the fine-tuned cytokine responsiveness of the SAA2 promoter, while exhibiting the quantitatively enhanced level of protein expression conferred by the tat/HIV element [4].

High impact information on SAA2

• Because only SAA2-derived products deposit in mouse amyloid tissues, the resistance of SJL mice to amyloidosis seems to be due to defective SAA2 gene expression [5].
• Furthermore, in amyloidosis-resistant SJL mice, the gene expression for one SAA isotype, SAA2, is defective, although SAA2 gene expression is normal in amyloidosis-susceptible BALB/c mice [5].
• The ratios of hepatic SAA2:SAA1 mRNA, as determined by in vitro translation, remained constant during the 20-d period, as did amounts of SAA1 and SAA2 synthesized and secreted by freshly isolated hepatocytes [6].
• Polymorphisms in the SAA2 or APOE gene did not appear to influence susceptibility to renal amyloidosis [7].
• A comparison of the nucleotide and deduced amino acid sequences of SAA1 cDNA with that of SAA2 cDNA showed a high degree of homology: 95% nucleotide sequence homology in the coding region (91% amino acid sequence homology) and 90% homology in the 3' untranslated region [8].

Biological context of SAA2

• To provide further evidence of an SAA superfamily gene cluster, an NcoI restriction fragment length polymorphism in the SAA2 gene was also typed through the CEPH reference panel.(ABSTRACT TRUNCATED AT 250 WORDS)[9]
• SAA1 and SAA2 genotypes had no significant effect on SAA levels [1].
• A further novel gene, SAA4, was isolated from a cosmid library and mapped 10 kb downstream of SAA2 [10].
• A putative glucocorticoid response element (GRE) is present (between residues -208 and -194) only in the SAA1 gene; a similar sequence in the corresponding region of the SAA2 gene is disrupted by a nine-residue insertion [11].
• Differential glucocorticoid enhancement of the cytokine-driven transcriptional activation of the human acute phase serum amyloid A genes, SAA1 and SAA2 [11].

Anatomical context of SAA2

• To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated [12].
• For instance, the sequence deduced for amino acids 1-12 (exon 2) has only 25% identity with human SAA1 and SAA2; it most closely resembles that of rabbit SAA3 isolated from synovial fibroblast cultures (75% identity) [13].
• In the human experimental system, IL-1beta induced transcription of acute-phase SAA (A-SSA; encoded by SAA1/SAA2) in primary chondrocytes [14].
• Here, we establish that the qualitative and kinetic aspects of SAA1 and SAA2 transcription following treatment of HepG2 hepatoma cells and KB epithelial cells with glucocorticoids and cytokines are quite distinct [15].
• As in the hepatoma cell line, co-stimulation of KB cells with glucocorticoids places SAA1 at a transcriptional advantage over SAA2 [15].

Associations of SAA2 with chemical compounds

• The application of the synthetic glucocorticoid dexamethasone in the context of cytokine stimulation enhanced the transcriptional activity of the SAA1, but not the SAA2, promoter such that readout from the former became equivalent to that from the latter [11].
• SAA5 and SAA2, respectively, lack one and three of the NH2-terminal residues common to SAA1 and SAA4 [16].
• cDNA clones encoding two major mouse serum amyloid A proteins, SAA1 and SAA2, were isolated from a liver cDNA library of the lipopolysaccharide-stimulated BALB/c mouse, and their nucleotide sequences were determined [8].
• Mink SAA2 also has valine in position 67, phenylalanine in position 71, and amino acid 105 is serine [17].
• Residue 10 in mink SAA2 is valine while arginine and asparagine are at positions 24 and 27, respectively, all characteristics of protein AA isolated from mink amyloid fibrils [17].

Regulatory relationships of SAA2

• The SAA2 alpha allele was predominant (approximately 90%) in both healthy controls and adult patients with rheumatoid arthritis [18].

Other interactions of SAA2

• The ninth spot was shown to contain a mixture of SAA1 alpha and SAA2 alpha [19].
• The six major spots corresponded to the Arg and des-Arg forms of SAA1 alpha and SAA2 alpha, respectively, and to the glycosylated and nonglycosylated form of constitutive serum amyloid A protein (C-SAA) [19].
• To study the cis-acting regulatory elements responsible for constitutive and IL-1-induced expression, DNA constructs containing varying lengths of the promoter region from the human SAA2 beta gene 5' to the bacterial reporter gene, chloramphenicol acetyltransferase (CAT), were generated and transfected into human hepatoma cells, HepG2 [20].
• The reciprocal treatment, i.e. stimulation of the promoter with IL-6 before IL-1 beta results in significantly less synergistic activation of the SAA2 promoter [21].

Analytical, diagnostic and therapeutic context of SAA2

• 1. Pulsed-field gel electrophoresis placed SAA1 to within 350 kb of the previously linked SAA2 and SAA4 genes [9].
• SAA1 and SAA2 gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) [1].
• Isoelectric focusing has demonstrated that SAA1 and SAA2 alpha are expressed but not SAA2 beta [22].
• In this study, we showed by Northern blot a synergistic induction of the acute phase protein gene SAA2 with a combination of deacetylase inhibitors (Trichostatin A or NaBu) and IL-1beta in the colon carcinoma cell line Caco-2 [23].
• In vitro evaluation of an enhanced human serum amyloid A (SAA2) promoter-regulated soluble TNF receptor fusion protein for anti-inflammatory gene therapy [4].

References