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饮食调节与大鼠黏膜五聚素(Mptx)蛋白结构预测及其在人类中的功能丧失

Dietary modulation and structure prediction of rat mucosal pentraxin (Mptx) protein and loss of function in humans.

机构信息

TI Food and Nutrition, RIKILT-Institute of Food Safety, Bornsesteeg 45, P.O box 230, 6700 AE, Wageningen, The Netherlands.

出版信息

Genes Nutr. 2007 Dec;2(3):275-85. doi: 10.1007/s12263-007-0058-x. Epub 2007 Oct 16.

Abstract

Mucosal pentraxin (Mptx), identified in rats, is a short pentraxin of unknown function. Other subfamily members are Serum amyloid P component (SAP), C-reactive protein (CRP) and Jeltraxin. Rat Mptx mRNA is predominantly expressed in colon and in vivo is strongly (30-fold) regulated by dietary heme and calcium, modulators of colon cancer risk. This renders Mptx a potential nutrient sensitive biomarker of gut health. To support a role as biomarker, we examined whether the pentraxin protein structure is conserved, whether Mptx protein is nutrient-sensitively expressed and whether Mptx is expressed in mouse and human. Sequence comparison and 3D modelling showed that rat Mptx is highly homologous to the other pentraxins. The calcium-binding site and subunit interaction sites are highly conserved, while a loop deletion and charged residues contribute to a distinctive "top" face of the pentamer. In accordance with mRNA expression, Mptx protein is strongly down-regulated in rat colon mucosa in response to high dietary heme intake. Mptx mRNA is expressed in rat and mouse colon, but not in human colon. A stop codon at the beginning of human exon two indicates loss of function, which may be related to differences in intestinal cell turnover between man and rodents.

摘要

黏膜五聚素(Mptx)是在大鼠中发现的一种短五聚素,其功能未知。其他亚家族成员包括血清淀粉样蛋白 P 成分(SAP)、C 反应蛋白(CRP)和 Jeltraxin。大鼠 Mptx mRNA 主要在结肠中表达,体内受膳食血红素和钙的强烈(30 倍)调节,这是结肠癌风险的调节剂。这使得 Mptx 成为肠道健康的潜在营养敏感生物标志物。为了支持作为生物标志物的作用,我们检查了五聚体蛋白结构是否保守,Mptx 蛋白是否受营养敏感表达,以及 Mptx 是否在小鼠和人类中表达。序列比较和 3D 建模表明,大鼠 Mptx 与其他五聚体高度同源。钙结合位点和亚基相互作用位点高度保守,而环缺失和带电残基有助于五聚体独特的“顶部”表面。与 mRNA 表达一致,高膳食血红素摄入会强烈下调大鼠结肠黏膜中的 Mptx 蛋白。Mptx mRNA 在大鼠和小鼠的结肠中表达,但在人类的结肠中不表达。人类外显子 2 起始处的一个终止密码子表明功能丧失,这可能与人类和啮齿动物之间肠道细胞更替的差异有关。

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本文引用的文献

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