Disease relevance of SAA4

• RT-PCR analysis confirmed the expression of the SAA1 and SAA4 genes in colon carcinomas, expression that was barely detectable in normal colon tissues [1].
• Here we underline the importance of ribosome binding site (rbs)-like sequences (also known as Shine-Dalgarno sequences) in the SAA4 cDNA for expression of recombinant SAA4 protein in Escherichia coli [2].
• Two differentially regulated size classes of C-SAA mRNA were detected in the hepatoma cell lines [3].

High impact information on SAA4

• The C-SAA octapeptide specifies the first two residues of a NSS tripeptide, the only potential N-linked glycosylation site in the molecule [4].
• SAA4 differed from the apolipoproteins in its ability to disrupt multilamellar dimyristoylphosphatidylcholine (DMPC) liposomes and generate bilayer discs [5].
• SAA4, however, increased turbidity at molar ratios of 1:250 and 1:100 even when preincubated in guanidine HCl before addition to liposomes [5].
• Using two-dimensional electrophoresis and phosphorimaging, SAA4 was found to be associated with a specific subpopulation of only three HDL particles, not involved in the initial cholesterol transfer from cells [6].
• During homeostasis, SAA4 is synthesized only in the liver [6].

Biological context of SAA4

• Fluorescence in situ hybridization analysis using a cosmid probe carrying the SAA2 and SAA4 genes refined the localization of these genes (and SAA1) to 11p15 [7].
• In addition, we have more fully characterized an ill-defined sequence previously misidentified by others as SAA4, which also maps to chromosome 11p and may represent a fifth SAA locus [8].
• The clone was described as the same as SAA4 and was characterized as a pseudogene [9].
• The corresponding vectors with the SAA4 upstream regulatory region served as controls [10].
• The extent of polyadenylation of A-SAA mRNA in ECV304 and KB cells differed whereas the polyadenylation of C-SAA mRNA remained constant [3].

Anatomical context of SAA4

• Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells [11].
• A-SAA has been shown to attract monocytes, neutrophils, and T lymphocytes, but the function of C-SAA remains to be determined [12].
• The presence of SAA4 mRNA and protein in macrophage-derived foam cells of coronary and carotid arteries suggested a specific role of human SAA4 during inflammation including atherosclerosis [2].
• C-SAA was detected in all hepatic and non-hepatic cell lines [3].

Associations of SAA4 with chemical compounds

• In this study, we developed an automated method for measuring SAA4 concentration in serum by kinetic nephelometry of anti-SAA4 antibody-coated latex agglutination [13].
• 'Acute phase' and 'constitutive' SAA (A-SAA and C-SAA, respectively) mRNA levels were measured in hepatic and non-hepatic cell lines after treatment with monocyte conditioned medium (MoCM), with or without dexamethasone (Dex) [3].

Other interactions of SAA4

• Median concentrations of A-SAA in serum and SF (44, 10 micrograms/ml) and CRP (46, 20 micrograms/ml), respectively, markedly differed from the mean values, whereas median concentrations of C-SAA (104, 85 micrograms/ml) and apo AI (1.17, 0.37 mg/ml), respectively, did not [12].

Analytical, diagnostic and therapeutic context of SAA4

• 1. Pulsed-field gel electrophoresis placed SAA1 to within 350 kb of the previously linked SAA2 and SAA4 genes [7].
• However, our restriction site and sequence analyses of SAA4 demonstrated that SAA4 and GSAA4 are separate entities [9].
• Novel isoforms of SAA4 were detected using ultracentrifugation combined with solid-phase extraction and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) [14].
• Here we show that PCR mutations of two rbs-like sequences in the human SAA4 cDNA promote expression of considerable amounts of recombinant SAA4 in E.coli [2].
• In subjects undergoing renal allograft transplantation, SAA4 changed in parallel with acute phase SAA, although its magnitude was not larger than a three-fold increase [15].

References