Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII
Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII
复制标题
DOI：
10.1111/j.1600-0463.2006.apm_461.x
复制
发表时间：
2006-07-01
期刊：
影响因子：
2.8
通讯作者：
Renkonen, Risto
中科院分区：
文献类型：
--
作者：
Niittymaki, Jaana;Mattila, Pirkko;Renkonen, Risto
L- focal是许多哺乳动物糖蛋白和糖脂的基本单糖成分。聚焦化需要GDP-L- focus作为聚焦的供体，并需要特异性聚焦转移酶（fuf - t）催化L- focus向各种乳胺受体分子的转移。GDP-L-聚焦物的生物合成包括两条途径。组成活性的新生途径包括通过gdp -d -甘露糖-4,6-脱水酶（GMD）和gdp -4-酮-6-脱氧-d -甘露糖-3,5-外聚酶-4-还原酶（FX）将细胞gdp -d -甘露糖转化为GDP-L-聚焦。在另一种生物合成途径中，在补救性代谢中，L-岩藻糖激酶（Fuk）从游离焦中合成L-焦-1-磷酸。L- focus -1-磷酸进一步被GDP-L- focus焦磷酸化酶（Fpgt）催化为GDP-L- focus。在细胞质溶胶中合成的GDP- l -焦点被特定的GDP-焦点转运蛋白（FUCT1）转移到高尔基体进行聚焦。含有α(1,3)-聚焦修饰的聚糖，如sialyl Lewis x型聚糖，在炎症和肿瘤发生中起重要作用。采用实时荧光定量PCR技术，研究了小鼠内皮细胞、巨噬细胞和淋巴肿瘤细胞中GDP- l-聚焦合成酶、GDP-聚焦转运蛋白和聚焦转移酶VII的mRNA表达水平。此外，以大鼠同种异体肾移植为模型系统，在急性炎症中检测到相同转录本的表达。我们的研究结果表明，在炎症和肿瘤发生过程中，GDP- l聚焦合成酶、GDP-聚焦转运蛋白和聚焦转移酶VII同时上调。
L-fucose is a fundamental monosaccharide component of many mammalian glycoproteins and glycolipids. Fucosylation requires GDP-L-fucose as a donor of fucose and a specific fucosyltransferase (Fuc-T) to catalyze the transfer of L-fucose to various lactosamine acceptor molecules. The biosynthesis of GDP-L-fucose consists of two pathways. The constitutively active de novo pathway involves conversion of cellular GDP-D-mannose to GDP-L-fucose by GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (FX). In the alternative biosynthetic pathway, in the salvage metabolism, L-fucokinase (Fuk) synthesizes L-fucose-1-phosphate from free fucose. L-fucose-1-phosphate is further catalyzed to GDP-L-fucose by GDP-L-fucose pyrophosphorylase (Fpgt). GDP-L-fucose, synthesized in the cytosol, is translocated to the Golgi for fucosylation by a specific GDP-fucose transporter (FUCT1). Glycans that contain alpha(1,3)-fucosylated modifications, e.g. sialyl Lewis X-type glycans, have an important role in inflammation and in tumorigenesis. We studied the mRNA expression levels of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII by quantitative real-time PCR in mouse endothelial cells, macrophages and lymphoid tumor cells. Moreover, the expression of the same transcripts was detected in acute inflammation using rat kidney allograft as model system. Our results indicate the simultaneous upregulation of the GDP-L-fucose synthesizing enzymes of the de novo pathway, GDP-fucose transporter and fucosyltransferase VII in inflammation and in tumorigenesis.