Hyper-acidic fusion minipeptides escort the intrinsic antioxidative ability of the pattern recognition receptor CRP in non-animal organisms
Hyper-acidic fusion minipeptides escort the intrinsic antioxidative ability of the pattern recognition receptor CRP in non-animal organisms
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高酸性融合小肽护航非动物体内模式识别受体 CRP 的内在抗氧化能力
DOI：
10.1038/s41598-019-39388-8
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发表时间：
2019
影响因子：
4.6
通讯作者：
Zou Zhurong
中科院分区：
文献类型：
--
作者：
Zhang Mengru;Liu Yanjuan;Liu Zhibin;Wang Jianmei;Gong Ming;Ge Hu;Li Xufeng;Yang Yi;Zou Zhurong
C-反应蛋白（CRP）被广泛用作炎症的生物标志物。它作为模式识别受体的一员，通过结合氧化特异性表位，包括脂质氧化链反应的一些中间产物，在天然免疫应答中发挥重要作用。CRP的抗氧化能力在体外研究中很少得到证实，尤其是在体内研究中还有待进一步研究。在此，我们在三种代表性的非动物生物体（大肠杆菌，酿酒酵母，烟草）中表达了人CRP，这些生物体本身缺乏CRP信号传导的环境，并发现CRP确实具有内在的抗氧化能力。异源CRP能增强重组大肠杆菌、酵母细胞和转基因烟草的抗氧化能力。我们还发现CRP的抗氧化作用与其溶解度呈正相关。只有可溶性CRP可以表现出明显的抗氧化活性，而CRP聚集体可能反而对细胞有毒（可能是促氧化）。此外，与超酸性小肽融合可以显著提高CRP的溶解度，同时保证或增强CRP的抗氧化能力。这些结果不仅为了解CRP相关炎症和疾病的病因提供了新的见解，而且还支持CRP生物技术在开发新的药物治疗和提高植物抗氧化性方面的应用潜力。
C-reactive protein (CRP) is widely used as a biomarker of inflammation. It plays important roles in innate immunity response as a member of pattern recognition receptors, by binding oxidation-specific epitopes including some intermediates of lipid oxidative chain reaction. The inferred antioxidative ability of CRP was ever demonstrated by only fewin vitroevidences, and needs to be clarified especiallyin vivo. Herein, we expressed human CRP in three representative non-animal organisms (Escherichia coli,Saccharomyces cerevisiae, and tobacco) inherently lacking the milieu for CRP signalling, and found CRP did possess an intrinsic antioxidative ability. Heterologous CRP could confer increased oxidative resistance in its recombinantE.coliand yeast cells and transgenic tobaccos. We also revealed a positive correlation between the antioxidative effect of CRP and its solubility. Only soluble CRP could exhibit distinct antioxidative activity, while the CRP aggregates might be instead toxic (probably pro-oxidative) to cells. Moreover, fusion with hyper-acidic minipeptides could remarkably improve CRP solubility, and meanwhile guarantee or enhance CRP antioxidative ability. These results not only provide a new insight for understanding the etiology of CRP-involved inflammations and diseases, and also endorse a potential of CRP biotechnological applications in developing new pharmaceutical therapies and improving plant oxidative resistance.