Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats
Increased expression of protein C-mannosylation in the aortic vessels of diabetic Zucker rats
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DOI：
10.1093/glycob/cwi012
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发表时间：
2005-04-01
期刊：
影响因子：
4.3
通讯作者：
Ito, Y
中科院分区：
文献类型：
--
作者：
Ihara, Y;Manabe, S;Ito, Y
C-甘露糖基化是蛋白质糖基化的一种新类型。有几个蛋白质的例子中，特定的基序Trp-X-X-Trp在第一个Trp被甘露糖化，从而产生C-甘露糖化Trp(CMW)。尽管C-甘露糖化修饰了Trp-X-X-Trp，被认为是细胞因子受体等多种整合蛋白的功能基序，但C-甘露糖化在细胞内的生理或病理意义尚不清楚。在这项研究中，为了表征生物样品中的C-甘露糖基化，我们用4个化学合成的CMW作为抗原，制备了针对CMW的特异性多克隆抗体。利用该抗体，我们研究了高血糖条件对培养细胞和糖尿病Zucker肥胖大鼠蛋白C-甘露糖化的影响。我们发现，与低糖条件相比，高血糖条件下巨噬细胞样RAW264.7细胞中蛋白C-甘露糖化水平增加。此外，Zucker肥胖大鼠的主动脉管壁C-甘露糖化增加.凝血酶敏感蛋白-1是一种经C-甘露糖化修饰的蛋白质，其在Zucker肥胖大鼠的主动脉组织中的表达也增加。这些结果表明，在高血糖条件下，特定组织或细胞类型的C-甘露糖化增加，提示C-甘露糖化增加在糖尿病并发症的发生中起到了病理作用。
C-Mannosylation is a novel type of glycosylation in proteins'. There are several examples of proteins in which the specific motif Trp-X-X-Trp is mannosylated at the first Trp to produce C-mannosylated Trp (CMW). Although C-mannosylation modifies Trp-X-X-Trp, predicted to be a functional motif of various integral proteins such as cytokine receptors, the physiological or pathological relevance of C-mannosylation in the cell is still not known. In this study, to characterize C-mannosylation in biological samples, we generated specific polyclonal antibodies against CMW by using 4 chemically synthesized CMW as an antigen. Using the antibody, we investigated the effect of hyperglycemic conditions on protein C-mannosylation in cultured cells and diabetic Zucker fatty rats. We found that protein C-mannosylation, was increased in macrophage-like RAW264.7 cells under hyperglycemic conditions compared to low-glucose conditions. Furthermore, C-mannosylation was increased in the, aortic vessel wall of Zucker fatty rats. Thrombospondin-1 was identified as a protein modified with C-mannosylation, and its expression was also increased in the aortic tissues of Zucker fatty rats. These results indicate that C-mannosylation is increased in specific tissues or cell types under hyperglycemic conditions, suggesting a pathological role for the increased C-mannosylation in the development of diabetic complications.