INVOLVEMENT OF ANNEXIN V IN THE ENDOTHELIAL APOPTOSIS INDUCED BY AUTOANTIBODIES.

膜联蛋白 V 参与自身抗体诱导的内皮细胞凋亡。

基本信息

项目摘要

Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. We have reported previously that plasma with LAC activity induces apoptosis in endothelial cells and binds annexin V. In this study, we separated two IgG antibody fractions, one with and one without affinity for annexin V, from 10 patients with LAC. LAC and apoptotic activities were localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation was dose-dependeub paralleling the amount of IgG added to the human umbilical vein endothelial cell culture medium, and was inhibited by preincubation with annexin V. Removal of the antiphospholipid antibodies from patient IgG with phospholipid liposomes did not abolish the apoptosis-inducing activities or binding to annexin V. These results imply that patients with LAC often have antibodies that do not bind phospholipids and are responsible for the induction of apoptosis in endothelial cells.Internucleosomal DNA fragmentation is generally perceived as one of the characteristic features of apoptosis, most of which are driven by caspase activation dependent upon ATP. On the other hand, ATP depletion has been reported to induce apoptosis accompanying DNA fragmentation. To address this apparent paradox, we analyzed the DNA: fragmenting activity generated in ATP-depleted cells. In HL-60 promyelocytic leukemia cells cultured in glucose-free medium with oligomycin, internucleosomal DNA fragmentation occurred as an early event. The DNA fragmentation was blocked by serine protease inhibitors but not by caspase inhibitors. Consistently, ICAD/DFF45 could not inhibit the DNA-fragmenting activity of the ATP depleted cytosol in a cell-free system. When ATP was supplied to the cell-free assay, 80% of the DNA-fragmenting activity was lost. The reduced activity was then restored by proteasome inhibitors, suggesting a role of proteasome to protect from a cellular insult derived from ATP-depletion
狼疮抗凝剂(LAC)与动脉和静脉血栓形成、血小板减少和复发性流产有关。我们以前曾报道过,血浆与LAC活性诱导内皮细胞凋亡,并结合膜联蛋白V。在这项研究中,我们分离出两个IgG抗体组分,一个与膜联蛋白V和一个没有亲和力,从10例LAC。LAC和细胞凋亡的活动都定位在所有10例患者的膜联蛋白V结合部分。DNA片段化呈剂量依赖性b,与加入人脐静脉内皮细胞培养基中的IgG量平行,用磷脂脂质体除去患者IgG中的抗磷脂抗体并不能消除细胞凋亡。这些结果意味着LAC患者通常具有不结合磷脂的抗体,核小体间DNA片段化通常被认为是细胞凋亡的特征之一,其中大多数是由依赖于ATP的半胱天冬酶激活驱动的。另一方面,据报道,ATP耗竭诱导凋亡伴随DNA片段化。为了解决这个明显的矛盾,我们分析了DNA:ATP耗竭细胞中产生的片段化活性。HL-60早幼粒细胞白血病细胞在无葡萄糖培养基中与寡霉素培养,核小体间DNA断裂发生作为一个早期事件。DNA断裂被丝氨酸蛋白酶抑制剂阻断,但不能被半胱天冬酶抑制剂阻断。在无细胞体系中,ICAD/DFF 45不能抑制ATP耗竭的胞液的DNA断裂活性。当ATP提供给无细胞测定时,80%的DNA片段化活性丧失。然后通过蛋白酶体抑制剂恢复降低的活性,这表明蛋白酶体的作用是保护细胞免受来自ATP耗尽的损伤

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nakamura, N and Wada, Y.: "Properties of DNA Fragmentation Activity Generated by ATP Depletion"Cell Death and Differentiation. (印刷中).
Nakamura, N 和 Wada, Y.:“ATP 耗竭产生的 DNA 片段活性的特性”细胞死亡和分化(正在出版)。
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和田芳直: "Annual Review免疫2004"中外医学社. 315(7) (2003)
和田义直:“免疫学年度评论 2004”,中外医学社 315(7) (2003)。
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Nakamura N, Wada Y.: "Properties of DNA fragmentation activity generated by ATP depletion."Cell Death Differ.. 7(5). 477-484 (2000)
Nakamura N,Wada Y.:“ATP 消耗产生的 DNA 片段化活性的特性。”细胞死亡差异.. 7(5)。
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Nakamura N, Wada Y: "Properties of DNA fragmentation activity generated by ATP depletion."Cell Death and Differentiation. 7. 477-484 (2000)
Nakamura N、Wada Y:“ATP 消耗产生的 DNA 片段化活性的特性。”细胞死亡和分化。
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Nakarnura N, Ban T, Yamaji K, Yoneda Y, Wada Y.: "Localization of the apoptosis inducing activity of lupus anticoagulant in an annexin V-binding antibody subset."J Clin Invest.. 101(9). 1951-1959 (1998)
Nakarnura N、Ban T、Yamaji K、Yoneda Y、Wada Y.:“狼疮抗凝剂在膜联蛋白 V 结合抗体子集中的细胞凋亡诱导活性的定位。”J Clin Invest.. 101(9)。
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WADA Yoshinao其他文献

WADA Yoshinao的其他文献

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{{ truncateString('WADA Yoshinao', 18)}}的其他基金

Glycoproteomic reasearch to reveal the frequency and diversity of the Congenital Disorders of Glycosylation
糖蛋白质组学研究揭示先天性糖基化障碍的频率和多样性
  • 批准号:
    23390081
  • 财政年份:
    2011
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Basic Research on Congenital Disorders of Glycosylation (CDG)
先天性糖基化障碍(CDG)的基础研究
  • 批准号:
    19390093
  • 财政年份:
    2007
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
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
  • 批准号:
    16390123
  • 财政年份:
    2004
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
INTERVENTION OF AUTOANTIBODY IN THE MEMBRANE PHOSPHOLIPID FLIP-FLOP OF TROPHOBLAST CELLS.
自身抗体对滋养层细胞膜磷脂触发器的干预。
  • 批准号:
    13670239
  • 财政年份:
    2001
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Protecting liver sinusoidal endothelial cells suppresses apoptosis in acute liver damage
保护肝窦内皮细胞抑制急性肝损伤时的细胞凋亡
  • 批准号:
    15K19870
  • 财政年份:
    2015
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    Grant-in-Aid for Young Scientists (B)
Molecular Regulation of Apoptosis in Endothelial Cells
内皮细胞凋亡的分子调控
  • 批准号:
    nhmrc : 1010638
  • 财政年份:
    2011
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    $ 1.6万
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    Project Grants
Investigating the role of endothelial cells (EC) in pulmonary arterial hypertension by controlled induction of EC apoptosis
通过控制内皮细胞 (EC) 凋亡的诱导来研究内皮细胞 (EC) 在肺动脉高压中的作用
  • 批准号:
    373962-2009
  • 财政年份:
    2010
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Postdoctoral Fellowships
Apoptosis of endothelial cells and extracellular matrix proteolysis: Roles in vascular healing and scarring
内皮细胞凋亡和细胞外基质蛋白水解:在血管愈合和疤痕形成中的作用
  • 批准号:
    210330
  • 财政年份:
    2010
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    $ 1.6万
  • 项目类别:
    Operating Grants
Investigating the role of endothelial cells (EC) in pulmonary arterial hypertension by controlled induction of EC apoptosis
通过控制内皮细胞 (EC) 凋亡的诱导来研究内皮细胞 (EC) 在肺动脉高压中的作用
  • 批准号:
    373962-2009
  • 财政年份:
    2009
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    $ 1.6万
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    Postdoctoral Fellowships
PROTECTIVE EFFECT OF SPHINGOSINE 1-PHOSPHATE ON LIVER SINUSOIDAL ENDOTHELIAL CELLS AGAINST ETHANOL-INDUCED APOPTOSIS
1-磷酸鞘氨醇对肝窦内皮细胞乙醇诱导的细胞凋亡的保护作用
  • 批准号:
    15590689
  • 财政年份:
    2003
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Role of Apoptosis in Alveolar Type II and Pulmonary Microvascular Endothelial Cells in the Inflammatory Response After Blunt Chest Trauma
II 型肺泡和肺微血管内皮细胞凋亡在胸部钝挫伤后炎症反应中的作用
  • 批准号:
    5408525
  • 财政年份:
    2003
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Priority Programmes
In situ detection of apoptosis in tumor endothelial cells
原位检测肿瘤内皮细胞凋亡
  • 批准号:
    6563959
  • 财政年份:
    2002
  • 资助金额:
    $ 1.6万
  • 项目类别:
Role of apoptosis of vascular endothelial cells In atherosclerosis
血管内皮细胞凋亡在动脉粥样硬化中的作用
  • 批准号:
    13470141
  • 财政年份:
    2001
  • 资助金额:
    $ 1.6万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
In situ detection of apoptosis in tumor endothelial cells
原位检测肿瘤内皮细胞凋亡
  • 批准号:
    6499809
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    2001
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    $ 1.6万
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