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

与ITI重链同源的新型血浆蛋白IHRP的功能研究

基本信息

批准号：
07672383
负责人：
MIURA Nanko
金额：
$ 1.41万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

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.

我发现了一种新的糖蛋白从硫酸葡聚糖柱的血浆置换治疗高血糖症患者。由于其氨基酸序列与ITI家族重链的氨基酸序列相似，故命名为IHRP（ITL family heavy chain-related protein）。ITI家族的重链含有DPHFII的氨基酸序列，其是通过硫酸软骨素与bikunin形成复合物所必需的。IHRP缺乏该序列，并且它不与bikunin形成复合物。IHRP基因定位于染色体3 p21-p14，ITI家族的重链1和3基因也存在于该染色体上。猪心脏缺血再灌注后，肝脏中IHRP mRNA呈急性时相蛋白样表达。人IHRP基因全长约15 kb，由24个外显子组成。该基因不含TATA盒，结构与ITI重链基因相似。启动子区有LF-A1、HNF-5、NF-IL-6和C/EBP。该基因位于EST基因的3 '端下游。用地塞米松和LPS处理后，炎症组织中均能诱导出小鼠IHRP，地塞米松能阻断TURP诱导的IHRP，而LPS则不能阻断。用小鼠IHRP基因启动子和经姜黄素处理后的小鼠肝细胞核提取物进行的凝胶位移试验显示了明显的凝胶位移，而正常肝提取物则没有。