GLYCOSYLATION OF GLYCOPROTEIN HORMONE FREE SUBUNIT DURING PREGNANCY: DEVELOPMENT
GLYCOSYLATION OF GLYCOPROTEIN HORMONE FREE SUBUNIT DURING PREGNANCY: DEVELOPMENT
批准号:
6123246
负责人:
DIANA L BLITHE
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-07-01 至 1999-06-30
中文摘要
。糖蛋白荷尔蒙a亚单位是
异源激素CG、LH、FSH和TSH。然而,在其免费的
形式,它是一种重要的胎盘和脑垂体产品,一直以来
被证明具有独立于二聚体激素的功能。
游离CC的糖基化与结合后的F7糖基化不同
形式。Cc和0的组合用于形成杂二聚体
在未成熟的多糖加工之前放置在内质网中。单位:毫升
尚未与0亚基结合的亚基,来自
翻译后糖基化机制可以接触到底物
通常由杂二聚体的0亚基保护的位点。
因此,oc亚基的自由形式通常包含更多
精心设计的低聚糖分支,以及更高数量的核心
岩藻糖化作用比从游离激素中获得的亚基更强。这些
特有的糖基化模式防止分泌游离(x
防止亚基与可能遇到的0亚基结合
细胞外,从而确保自由(x分子)的数量。这个
(X亚基是胎盘的主要产物,其糖基化是
发现在怀孕的过程中发生了巨大的变化。在……里面
这次合作,我们分析了五个方面的糖基化变化
正常怀孕。ESI NIS的研究表明,
核心岩藻糖化,以及糖链支化的变化。这个
还用高pH阴离子交换层析法测定了多糖
和CID MS/N4S。核岩藻糖化和三天线的量
从妊娠早期到中期,葡聚糖显著增加,
并观察到了从1-4/1-3到捕食的转变
1-6/1-6-分枝三天线结构。糖基化的变化
在同一孕期接受检查的所有个体中都会发生,
提示发育调节
N-乙酰氨基葡萄糖转移酶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
影响滋养层细胞的恶变。调查结果
对提议使用特定形式的
作为癌症标志物的糖基化,如这些物质的相对量
正常妊娠中的糖链将由胎龄决定。
英文摘要
. 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.
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GLYCOPROTEIN HORMONES: OLIGOSACCHARIDE STRUCTURE & FUNCTION
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批准号:6254127
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项目类别:
-
资助金额:$1.96万
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财政年份:1997
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负责人:DIANA L BLITHE
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依托单位:
GLYCOPROTEIN HORMONES: OLIGOSACCHARIDE STRUCT & FUNCT: PREGNANCY RELATED HORMONE
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批准号:5225901
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:DIANA L BLITHE
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