Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes
Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes
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DOI：
10.1096/fj.07-104257
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发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Neelamegham, Sriram
中科院分区：
文献类型：
--
作者：
Marathe, Dhananjay D.;Chandrasekaran, E. V.;Neelamegham, Sriram
系统生物学方法在新兴的糖组学领域的应用需要在基因和酶水平上收集和整合糖基转移酶数据，以产生假说。我们系统地研究了不同系统中基因表达、糖基转移酶活性、糖链表达和选择素结合功能之间的关系，包括人中性粒细胞、未分化的HL-60(人早幼粒细胞)、分化的HL-60和特定生长阶段同步的HL-60。结果表明：1)SLE(X)(sialyl-Lewis-X)表位在中性粒细胞P-选择素糖蛋白配体-1(PSGL-1)上的表达水平高于HL-60。这种差异可能是由于这两种细胞中α-1，3-岩藻糖基转移酶和α-2，3-唾液酸基转移酶的相对活性不同所致。2)HL-60细胞沿粒系分化后，β1，4GalT和β1，3GlcNAcT活性增加1.6~3.2倍。这可能有助于LacNAc链的延伸，分化后与细胞结合的DSA-凝集素(凝集素识别LacNAc)增加了1.7倍。3)促进白细胞中SLeX形成的酶的活性可能随着ST3[Galβ1，4GlcNAc]的变化而变化
The application of systems biology methods in the emerging field of glycomics requires the collection and integration of glycosyltransferase data at the gene and enzyme level for the purpose of hypothesis generation. We systematically examined the relationship between gene expression, glycosyltransferase activity, glycan expression, and selectin-binding function in different systems, including human neutrophils, undifferentiated HL-60 (human promyelocytic cells), differentiated HL-60, and HL-60 synchronized in specific growth phases. Results demonstrate that 1) the sLe(X) (sialyl-Lewis-X) epitope is expressed in P-selectin glycoprotein ligand-1 (PSGL-1) from neutrophils at higher levels compared with HL-60. This variation may be due to differences in the relative activities of alpha 1,3-fucosyltransferases and alpha 2,3-sialyltransferases in these two cell types. 2) HL-60 cell differentiation along granulocyte lineage increased the activity of beta 1,4GalT and beta 1,3GlcNAcT by 1.6- to 3.2-fold. This may contribute to LacNAc chain extension as evidenced by the 1.7-fold increase in DSA-lectin (lectin recognizing LacNAc) binding to cells after differentiation. 3) The activity of enzymes contributing to sLeX formation in leukocytes likely varies as ST3[Gal beta 1,4GlcNAc]