权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Antiphospholipid syndrome : Elucidation of molecular mechanism to give insights into new therapeutic approach

抗磷脂综合征：阐明分子机制以深入了解新的治疗方法

基本信息

批准号：
16390123
负责人：
WADA Yoshinao
金额：
$ 9.34万
依托单位：
Osaka Medical Center and Research Institute for Maternal and Child Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

It is generally accepted that the primary event of antiphohpholipid syndrome (APS) is the activation of the complement system. We carried out a proteomic analysis of the plasma proteins that are binding to negatively charged phospholipids, cardiolipin (CL) or phosphatidylserine (PS), and are thus potentially involved in the pathogenesis. The plasma proteins recovered from an Octyl-Sepharose column, in which CL or PS was embedded, were separated by two-dimensional electrophoresis. By peptide mass fingerprinting, factor H, factor H-related protein-1, IHRP, Complement 4, complement C1q and beta2 glycoprotein I were identified. A group of APS patients was demonstrated to have anti-factor H antibodies, but a close link of anti-factor H to the thrombotic or obstetric complications was not clearly demonstrated. These proteins are now being studied for their capability of inducing hemolysis of rabbit reticulocytes in the presence of antiphospholipid IgG from the APS patients.Miscarriage is one … More of the complications found in APS patients. From this point of view, implantation may be a target of antiphospholipid antibodies. Matrix metalloproteinases (MMPs) have been implicated in embryonal implantation processes such as trophoblast invasion and decidualization. Therefore, temporal and spatial distributions of MMP bioactivities were analyzed by in situ zymography, which indicated these activities to be markedly increased in the post-coital mouse uterus as compared with the later implantation stage. Activity was ascribed to proMMP9, which moved from the uterine serosa to the endometrium but was not associated with mRNA upregulation. The activity was co-localized with infiltrating neutrophils, and neutropenic mice did not exhibit MMP9 expression. Removing the seminal vesicles from male mice abolished the post-coital increase in MMP9 in the female. These results indicate the major MMP activity in the preimplantation uterus to originate in proMMP9-bearing neutrophils attracted by seminal plasma. Considering our results together with those of previous reports of reduced fertility in Mmp9-deficient female mice, we speculate that neutrophil infiltration participates in the extracellular matrix degradation needed to support pregnancy. Less

一般认为抗磷脂综合征（APS）的主要事件是补体系统的激活。我们进行了蛋白质组学分析的血浆蛋白结合带负电荷的磷脂，心磷脂（CL）或磷脂酰丝氨酸（PS），因此可能参与发病机制。从包埋CL或PS的Octyl-Sepharose柱回收的血浆蛋白通过双向电泳分离。通过肽质量指纹图谱，鉴定了因子H、因子H相关蛋白-1、IHRP、补体4、补体C1 q和β 2糖蛋白I。一组APS患者被证明有抗H因子抗体，但抗H因子与血栓形成或产科并发症的密切联系尚不清楚。目前正在研究这些蛋白质在来自APS患者的抗磷脂IgG存在下诱导兔网织红细胞溶血的能力。 ...更多信息 APS患者中发现的并发症。从这个角度来看，着床可能是抗磷脂抗体的靶点。基质金属蛋白酶（MMPs）参与胚胎着床过程，如滋养层浸润和蜕膜化。因此，MMP生物活性的时间和空间分布进行了分析，原位酶谱，这表明这些活动显着增加，在交配后小鼠子宫相比，后期植入阶段。活动归因于proMMP 9，其从子宫浆膜移动到子宫内膜，但与mRNA上调无关。该活性与浸润性中性粒细胞共定位，并且血小板减少小鼠没有表现出MMP 9表达。去除雄性小鼠的精囊后，雌性小鼠交配后MMP 9的增加消失了。这些结果表明，在着床前子宫中的主要MMP活性起源于由精浆吸引的携带proMMP 9的中性粒细胞。考虑到我们的研究结果与Mmp 9缺陷的雌性小鼠生育能力降低的先前报告，我们推测中性粒细胞浸润参与支持妊娠所需的细胞外基质降解。少

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mass spectrometry for congenital disorders of glycosylation, CDG

DOI：
10.1016/j.jchromb.2006.02.028
发表时间：
2006-06-21
期刊：
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
影响因子：
3
作者：
Wada, Yoshinao
通讯作者：
Wada, Yoshinao

Determination of unique amino acid substitutions in protein variants by peptide mass mapping with FT-ICR MS

通过 FT-ICR MS 肽质量图谱确定蛋白质变体中的独特氨基酸取代