Disease relevance of Saa3

• Regulation of mouse serum amyloid A3 gene expression during acute phase reaction [1].
• Our results also showed the expression of SAA3 mRNA, in liver and heart from animals in the acute phase of Chagas disease [2].
• Recently, serum amyloid A3 (SAA3) has been characterized as an adipocyte-secreted acute-phase reactant, expression of which is dramatically increased in insulin resistance and obesity [3].

High impact information on Saa3

• In contrast, expression from the SAA3 promoter was found only in liver and was much more responsive to LPS than to turpentine [4].
• Murine serum amyloid A3 is a high density apolipoprotein and is secreted by macrophages [5].
• Furthermore, pro-inflammatory stimuli and high glucose can lead to the induction of SAA3 in adipose tissue in vivo as well as in the 3T3-L1 adipocyte cell line [6].
• NFkappa B interacts with serum amyloid A3 enhancer factor to synergistically activate mouse serum amyloid A3 gene transcription [7].
• Intriguingly, no consensus NFkappaB-binding site was found in the SAA3 promoter region; rather a putative NFkappaB-binding sequence with 3-base pair mismatches was identified in the DRE [7].

Biological context of Saa3

• We have located Saa4 11 kb upstream from Saa3 and 5 kb downstream from Saa1, with the pseudogene approximately 1 kb from the 5' end of Saa4 [8].
• DNA sequence analysis identified clone C122 as murine serum amyloid A 3 (Saa3), a member of the Saa family of acute-phase or inflammatory response genes [9].
• A 20-fold induction of serum amyloid A3 mRNA by O(3) suggested activation of NF-kappaB and CCAAT/enhancer binding protein-mediated pathways by inflammatory cytokines [10].
• In both transient DNA transfection assays and BNL cells stably transformed with SAA3 fusion genes, deletion analysis of the SAA3 promoter indicates that sequences between -185 and -138 base pairs 5' to the transcription initiation site are essential for expression of heterologous genes [11].
• We have employed a mouse liver-derived cell line (BNL) to identify DNA sequences in the promoter of the serum amyloid A3 (SAA3) gene essential for expression [11].

Anatomical context of Saa3

• Semi-quantitative reverse transcription-polymerase chain reaction revealed a 15-20-fold increase in Saa3 message levels in the bone marrow of irradiated mice from 3 days to 2 weeks after exposure [9].
• SAA3 is a novel gene in granulosa cells with yet unknown functions in the ovary [12].
• Additionally, we show SAA3 is expressed at low levels under normal conditions but in the diabetic state is dramatically up-regulated in adipose tissue while down-regulated in liver [6].

Associations of Saa3 with chemical compounds

• The application of an AR inhibitor, SNK-860, to the high glucose medium ameliorated the increased sorbitol and fructose contents and the reduced AKR1A4 mRNA expression, while it had no effect on mRNA expressions for SAA3, ANGPTL4 or Evi3 [13].
• Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes [3].
• In contrast, insulin, isoproterenol and growth hormone did not influence SAA3 synthesis [3].

Regulatory relationships of Saa3

• Tumor necrosis factor-alpha induces serum amyloid A3 in mouse granulosa cells [12].
• Overexpression of the inhibitor of NF-kappaB (called IkappaB) blocked SAA3 promoter activity induced by TNF and by p65 in OV3121-1 cells [12].

Other interactions of Saa3

• Closer analysis of deletion mutants of the SAA3 promoter revealed the necessity of a NF-kappaB like site for responsiveness to TNF in the OV3121-1 cells [12].
• Serum amyloid A3 and L-selectin mRNAs were elevated as early as 20 days after intracerebral inoculation [14].

Analytical, diagnostic and therapeutic context of Saa3

• TNF also increased phospho-IkB and SAA3 in whole-cell homogenates as determined by Western blots [12].
• Among the different PCR product bands identified in the differential display gel, one showed high homology with the serum amyloid A3 protein (SAA3) [2].
• Northern blot assays showed augmentation of SAA3 mRNA expression by inflammatory macrophages exposed to live trypomastigotes or parasite glycolipids, as compared to unstimulated macrophages [2].

References