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人体组织和血液中存在人C反应蛋白的多聚体异构体。

Presence of multimeric isoforms of human C-reactive protein in tissues and blood.

作者信息

Li Qiling, Xu Wei, Xue Xue, Wang Qi, Han Lu, Li Wenzhi, Lv Shulan, Liu Dong, Richards Jendai, Shen Zhujun, Ma Li, Song Qing

机构信息

Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.

出版信息

Mol Med Rep. 2016 Dec;14(6):5461-5466. doi: 10.3892/mmr.2016.5922. Epub 2016 Nov 3.

Abstract

The baseline concentration of C-reactive protein (CRP) has been associated with a wide array of human diseases. In epidemiological studies and in the clinic, CRP is typically measured as a pentamer, composed of 5 identical CRP subunits. The present study aimed to determine whether other isoforms were present in the blood by examining CRP conformations. Transgenic rats expressing human CRP under the mouse albumin promoter were generated and genotyped. Non‑reducing western blotting was performed using the blood and tissues of transgenic rats and human patients. CRP concentrations in human blood were examined by enzyme‑linked immunosorbent assay. In addition to the pentameric isoform, CRP was detected as a trimer and tetramer in the blood of human CRP transgenic rats. Furthermore, trimeric and tetrameric CRP was observed in various tissues, including aorta, liver, kidney, pancreas, heart and skeletal muscle. Notably, these two isoforms appeared to be age‑associated, as they were detected only in the blood and tissues of older transgenic rats. The existence of additional CRP isoforms was confirmed in the blood of human patients by non‑reducing western blotting. Clinical and epidemiological studies typically focus on CRP concentration. However, the results of the present study suggest that, in addition to concentration, CRP conformation may require analysis.

摘要

C反应蛋白(CRP)的基线浓度与多种人类疾病相关。在流行病学研究和临床中,CRP通常作为由5个相同CRP亚基组成的五聚体进行测量。本研究旨在通过检测CRP构象来确定血液中是否存在其他异构体。生成了在小鼠白蛋白启动子控制下表达人CRP的转基因大鼠并进行基因分型。使用转基因大鼠和人类患者的血液及组织进行非还原蛋白质印迹分析。通过酶联免疫吸附测定法检测人血液中的CRP浓度。除了五聚体异构体,在人CRP转基因大鼠的血液中还检测到了三聚体和四聚体形式的CRP。此外,在包括主动脉、肝脏、肾脏、胰腺、心脏和骨骼肌在内的各种组织中也观察到了三聚体和四聚体CRP。值得注意的是,这两种异构体似乎与年龄相关,因为它们仅在老年转基因大鼠的血液和组织中被检测到。通过非还原蛋白质印迹分析证实了人类患者血液中存在其他CRP异构体。临床和流行病学研究通常关注CRP浓度。然而,本研究结果表明,除了浓度外,CRP构象可能也需要进行分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b59d/5355649/40ed1b358205/MMR-14-06-5461-g00.jpg

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