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

我从血浆置换的葡聚糖硫酸酯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，故将其命名为IHRP(ITL家族重链相关蛋白)。ITI家族的重链含有DPHFII的氨基酸序列，DPHFII是通过硫酸软骨素与Bikunin形成复合体所必需的。IHRP缺乏这一序列，而且它不是来自与bikunin的复合体。IHRP基因位于染色体3p21-p14上，其上还含有ITI家族重链基因1和3。猪IHRP mRNA在心脏缺血再灌流后的肝脏中像急性时相蛋白一样被诱导。人IHRP基因全长约15kb，由24个外显子组成。该基因没有TATA盒，结构与ITI重链基因相似。启动子区域有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可诱导小鼠炎症反应，松节油的诱导可被地塞米松阻断，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细胞核提取液进行凝胶漂移分析，结果显示有明显的凝胶漂移，而正常肝提取液则没有。

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.