Study on the function of a novel plasma protein IHRP which has a homology to ITI heavy chain

我从血浆分离法硫酸葡聚糖柱洗脱液中发现了一种新的糖蛋白，用于治疗高胆固醇血症患者。由于其氨基酸序列与ITI家族重链相似，笔者将其命名为IHRP （ITL家族重链相关蛋白）。ITI家族的重链含有DPHFII氨基酸序列，这是通过硫酸软骨素与比库宁形成络合物所必需的。IHRP缺乏这一序列，也不与bikunin形成复合物。IHRP基因位于染色体3p21-p14上，其上也存在ITI家族重链1和重链3基因。心脏缺血再灌注后，肝脏中IHRP mRNA像急性期蛋白一样被诱导表达。人类IHRP基因扩增约15 kb，由24个外显子组成。该基因无TATA盒，结构与ITI重链基因相似。启动子区存在LF-A1、HNF-5、NF-IL6和C/EBP。该基因位于EST基因的3'下游。松节油或LPS均可诱导小鼠IHRP发生炎症反应。地塞米松能阻断松节油诱导，而脂多糖则不能。用小鼠IHRP基因启动子和松节油处理后的小鼠肝脏核提取物进行凝胶转移实验，发现有明显的凝胶转移，而正常肝脏提取物则没有。

I discovered a novel glycoprotein from the eluate of the dextran sulfate column of plasmapheresis for the treatment of hypercholesteremia patients. Because its amino acide sequence was similar to those of the heavy chains of ITI family, I named its IHRP (ITL family heavy chain-related protein). The heavy chains of ITI family contained the amino acid sequence of DPHFII which is necessary for the complex formation with bikunin via chondroitin sulfate. IHRP lacks this sequence and it does not from a complex with bikunin. The IHRP gene located on chromosome 3p21-p14, on which the genes of heavy chain 1 and 3 of ITI family also exsted. Porcine IHRP mRNA was induced like acute-phase protein in the liver after the heart ischemia and reperfusion. Human IHRP gene expanded in about 15 kb and consisted of 24 exons. The gene had no TATA box and similar structure to that of ITI heavy chain gene. There were LF-A1, HNF-5, NF-IL6 and C/EBP on the promotor region. The gene was located at the 3'down-stream of EST gene. Mouse IHRP was induced in the inflammation after the treatment with turpentine or LPS.The induction with turpentine was blocked with dexamethason but it with LPS was not. The gel-shift assay with mouse IHRP gene promotor and the nuclear extract from the mouse liver after the turpentine treatment showed the clear gel-shift, however, the extract from the normal liver did not.