GLYCOSYLATION OF GLYCOPROTEIN HORMONE FREE SUBUNIT DURING PREGNANCY: DEVELOPMENT

妊娠期间糖蛋白无激素亚基的糖基化：发育

• 批准号: 6123246
• 负责人: DIANA L BLITHE
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123246
• 关键词: biological products; biomaterials; biomedical resource; carbohydrates; female; growth /development; hormones; human subject; human tissue; lymphatic system; mother /infant health care; reproductive system; structural biology

. The glycoprotein hormone a subunit is common to the heterodi-ineric hormones CG,LH, FSH, and TSH. However, in its free form, it is an important placental and pituitary product and has been shown to have functions that are independent of the dimeric hormones. Glycosylation of free cc differs fi7om glycosylation of the combined form. The combination of cc and0 for heterodimer formation takes place in the ER prior to processing of the immature glycans. In cc subunits that have not combined with a 0 subunit, enzymes from the post-translational glycosylation machinery have access to substrate sites that are normally protected by the0 subunit of the heterodimer. As a result, the free form of oc subunit generally contains more elaborate oligosaccharide branching, as well as higher amounts of core fucosylation than a subunit obtained from dissociated hormone. These characteristic glycosylation patterns prevent secreted free (x subunits from combining with 0 subunits that might be encountered extracellularly, thus ensuring a population of free (x molecules. The (x subunit is a major placental product and its glycosylation was found to change dramatically during the advancement of pregnancy. In this collaboration, we have analyzed the glycosylation changes in five normal pregnancies. ESI NIS studies have indicated higher core-fucosylation, as well as changes in branching of glycans. The glycans were also determined by high-pH anion-exchange chromatography and CID MS/N4S. Amounts of core-fucosylation and of triantennary glycans increased substantially from early to late second trimester, and a shift was observed from 1-4/1-3 toward predom~inantly 1-6/1-6-branched triantennary structures. The glycosylation changes occurred in all individuals examined at the same gestational period, suggesting developmental regulation of N-acetylglucosaminyl-transferases IV and V, and a 6-fucosyltransferase during normal pregnancy. These enzymatic activities also appear to be affected in malignant transformation of the trophoblast. The findings have important implications for the proposed use of specific forms of glycosylation as markers for cancer, as the relative amounts of these glycans in normal pregnancy will be determined by gestational age.

. 糖蛋白激素a亚单位是共同的， 异源二系激素CG、LH、FSH和TSH。 然而，在其自由 形式，它是一个重要的胎盘和垂体产品， 显示其功能不依赖于二聚体激素。 游离CC的糖基化不同于组合CC的糖基化。 form. 用于异二聚体形成的cc和0的组合需要 在处理未成熟聚糖之前将其置于ER中。 连铸 未与0亚基结合的亚基， 翻译后糖基化机制可接近底物 通常被异二聚体的0亚基保护的位点。 因此，α亚基的游离形式通常含有更多的 精细的寡糖分支，以及更高量的核心 岩藻糖基化比从解离的激素获得的亚基。 这些 特征性糖基化模式阻止分泌游离（x 子单元与可能遇到的0个子单元组合 细胞外，从而确保游离β分子的群体。 的 （x亚基是胎盘的主要产物，其糖基化是 在怀孕的过程中发生了巨大的变化。 在 通过这项合作，我们分析了五种糖基化的变化， 正常怀孕 ESI NIS研究表明， 核心岩藻糖基化以及聚糖分支的变化。 的 还通过高pH阴离子交换色谱法测定聚糖 和CID MS/N4S。 核心岩藻糖基化和三触角 聚糖从早期到晚期中期妊娠显著增加， 从1-4/1-3向优势转化 1-6/1-6分支三触角结构。 糖基化改变 发生在同一妊娠期检查的所有个体中， 这表明， N-乙酰葡糖胺基转移酶IV和V，以及6-岩藻糖基转移酶 在正常怀孕期间。 这些酶活性似乎也是 在滋养层的恶性转化中受到影响。 这些发现 对拟议使用的特定形式的 糖基化作为癌症的标志物，作为这些糖基化的相对量， 正常妊娠中的聚糖将通过胎龄来确定。