Meek R L, Benditt E P
Department of Pathology, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1989 Mar;86(6):1890-4. doi: 10.1073/pnas.86.6.1890.
Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation--e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of approximately 400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extra-hepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of approximately 400 and approximately 500 nucleotides in length. Liver SAA1/SAA2-related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide- and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates.
血清淀粉样蛋白A(SAA)是一种在哺乳动物中发现的高密度脂蛋白的小(12 kDa)急性期载脂蛋白。它也是淀粉样蛋白A的前体,淀粉样蛋白A是慢性或复发性炎症(如类风湿性关节炎)继发的淀粉样变性中发现的纤维的主要蛋白质成分。然而,大鼠不会发生淀粉样变性,并且SAA不是大鼠高密度脂蛋白的载脂蛋白;因此,就SAA基因的表达而言,大鼠似乎是个例外。我们在此报告,大鼠确实拥有SAA基因家族的代表,并表达两种不同的SAA mRNA。此外,组织中表达的基因模式及其受炎症因子的诱导情况与相关小鼠基因相似。用SAA cDNA和针对三种小鼠SAA基因的互补RNA探针通过RNA印迹杂交法检测正常和受伤大鼠各种组织的RNA。与小鼠SAA1和SAA2 mRNA相关的约400个核苷酸的SAA mRNA在注射细菌脂多糖后24小时在肝脏中达到高水平。未发现肝外组织表达与SAA1/SAA2相关的mRNA。松节油诱导出两种长度约为400和500个核苷酸的肝脏SAA1/SAA2相关mRNA。从注射脂多糖和松节油的大鼠肝脏中选择并在麦胚蛋白质合成系统中翻译的与SAA1/SAA2相关的mRNA产生了一种估计分子量为8 kDa的单一蛋白质。这种大鼠肝脏SAA相关mRNA似乎缺乏两个两亲性螺旋结构域部分和连接序列的高度保守编码区。发现与小鼠SAA3相关的mRNA在脂多糖注射后在肺中高水平表达,但松节油注射后未表达。这种mRNA在对照大鼠的回肠和大肠中也高水平表达,在对照或受攻击大鼠的肝脏中未发现。这些观察结果表明,SAA基因家族在大鼠中存在并表达,并且其表达在与小鼠相似的情况下被发现。这支持了SAA基因家族在脊椎动物对损伤反应中的重要性。