Rudnick C M, Dowton S B
Edward Mallinkrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1993 Oct 15;268(29):21760-9.
The structure and expression of the gene encoding serum amyloid P (SAP) component of the Syrian hamster have been studied by isolation of cosmid clones, nucleotide sequence analyses, and quantitation of nuclear run-on transcripts, nuclear RNA, mRNA, and protein levels. Hamster SAP, originally identified as female protein (FP), is a unique pentraxin because pretranslational expression of this gene is modulated by mediators of inflammation and sex steroids. SAP(FP) levels are high in sera from female hamsters and low in males. The response to inflammation is divergent; SAP(FP) levels decrease in females and increase in males during an acute phase response. The SAP(FP) gene encodes a 211 amino acid residue mature polypeptide as well as a 22-residue signal peptide. The intron/exon organization is similar to that of other pentraxins, but additional transcripts are generated from alternate polyadenylation sites in the 3' region. Circulating levels of SAP(FP) and the corresponding hepatic transcript levels are augmented by estrogen, while testosterone, dexamethasone, and progesterone cause a decrease in these levels. In addition the cytokines interleukin-1, -6, and tumor necrosis factor mediate a decrease in hepatic SAP(FP) transcript levels in female hamsters but did not cause a significant elevation of SAP(FP) mRNA in livers of male hamsters. The differences in expression of the SAP(FP) gene between male and female hamsters and between unstimulated male hamsters and male hamsters stimulated with an injection of lipopolysaccharide are due, at least in part, to alterations in transcription.
通过分离黏粒克隆、进行核苷酸序列分析以及对核转录本、核RNA、mRNA和蛋白质水平进行定量分析,研究了叙利亚仓鼠血清淀粉样蛋白P(SAP)成分编码基因的结构和表达。仓鼠SAP最初被鉴定为雌性蛋白(FP),是一种独特的五聚体蛋白,因为该基因的翻译前表达受炎症介质和性类固醇的调节。雌性仓鼠血清中SAP(FP)水平高,雄性中低。对炎症的反应是不同的;在急性期反应期间,雌性仓鼠的SAP(FP)水平降低,而雄性升高。SAP(FP)基因编码一个211个氨基酸残基的成熟多肽以及一个22个残基的信号肽。内含子/外显子组织与其他五聚体蛋白相似,但在3'区域的可变聚腺苷酸化位点产生额外的转录本。雌激素可提高循环中SAP(FP)水平以及相应的肝脏转录本水平,而睾酮、地塞米松和孕酮则导致这些水平降低。此外,细胞因子白细胞介素-1、-6和肿瘤坏死因子可介导雌性仓鼠肝脏中SAP(FP)转录本水平降低,但不会导致雄性仓鼠肝脏中SAP(FP)mRNA显著升高。雄性和雌性仓鼠之间以及未刺激的雄性仓鼠和注射脂多糖刺激的雄性仓鼠之间SAP(FP)基因表达的差异至少部分归因于转录的改变。