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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulatory Effects Of Ferritin On Angiogenesis
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Regulatory Effects Of Ferritin On Angiogenesis

机译：铁蛋白对血管生成的调节作用

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摘要

Angiogenesis, the synthesis of new blood vessels from preexisting vessels, plays a critical role in normal wound healing and tumor growth. HKa (cleaved high molecular weight kininogen) is an endogenous inhibitor of angiogenesis formed by the cleavage of kininogen on endothelial cells. Ferritin is a protein principally known for its central role in iron storage. Here, we demonstrate that ferritin binds to HKa with high affinity (K_d 13 nM). Further, ferritin antagonizes the antiangiogenic effects of HKa, enhancing the migration, assembly, and survival of HKa-treated endothelial cells. Effects of ferritin were independent of its iron content. Peptide mapping revealed that ferritin binds to a 22-aa subdomain of HKa that is critical to its antiangiogenic activity. In vivo, ferritin opposed HKa's antiangiogenic effects in a human prostate cancer xenograft, restoring tumor dependent vessel growth. Ferritin-mediated regulation of angiogenesis represents a new angiogenic regulatory pathway, and identifies a new role for ferritin in cell biology.
机译：血管生成是由先前存在的血管合成的新血管，在正常伤口愈合和肿瘤生长中起关键作用。 HKa（裂解的高分子量激肽原）是血管生成的内源性抑制剂，是由内皮细胞上激肽原的裂解形成的。铁蛋白是一种蛋白质，主要因其在铁存储中的核心作用而闻名。在这里，我们证明铁蛋白以高亲和力（K_d 13 nM）结合HKa。此外，铁蛋白拮抗HKa的抗血管生成作用，增强了HKa处理的内皮细胞的迁移，组装和存活。铁蛋白的作用与其铁含量无关。肽图分析显示，铁蛋白结合HKa的22-aa子域，这对它的抗血管生成活性至关重要。在体内，铁蛋白对抗人前列腺癌异种移植物中HKa的抗血管生成作用，恢复了肿瘤依赖性血管的生长。铁蛋白介导的血管生成调节代表了新的血管生成调节途径，并确定了铁蛋白在细胞生物学中的新作用。

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  • 作者

    Lan G. Coffman; Derek Parsonage; Ralph DAgostino Jr.; Frank M. Torti; Suzy V. Torti;

  • 作者单位

    Program in Molecular Medicine, Wake Forest University School of Medicine, Winston Salem NC 27157;

    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem NC 27157;

    Comprehensive Cancer Center Wake Forest University School of Medicine, Winston Salem NC 27157 Department of Public Health Sciences, Section on Biostatistics, Wake Forest University School of Medicine, Winston Salem NC 27157;

    Comprehensive Cancer Center Wake Forest University School of Medicine, Winston Salem NC 27157 Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem NC 27157;

    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem NC 27157 Comprehensive Cancer Center Wake Forest University School of Medicine, Winston Salem NC 27157;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    iron; kininogen;

    机译：铁;激肽原;

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