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Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death
https://repo.qst.go.jp/records/48152
https://repo.qst.go.jp/records/48152163055a2-929e-440a-8d1b-6b9076d5d677
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-07-24 | |||||
タイトル | ||||||
タイトル | Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Hazawa, Masaharu
× Hazawa, Masaharu× Yasuda, Takeshi× Saotome-Nakamura, Ai× Tomiyama, Kenichi× Chizuka, Obara× Goto, Takaya× Katsushi, Tajima× 羽澤 勝治× 安田 武嗣× 富山 健一× 小原 千寿香× 後藤 孝也× 田嶋 克史 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Plasminogen activator inhibitor-1 (PAI-1) is induced by radiation resulting in endothelial cell impairment, potentially leading to multiple organ failure. Vitronectin (VN) is a 75-kDa glycoprotein (VN75) cleaved into two forms (VN75 or VN65/10) by furin, which is regulated by intracellular PAI-1. VN protects against radiation-induced endothelial cell death, but the mechanisms involved in VN processing and its interactions with intra- and extracellular PAI-1 remain unclear. We examined these processes in cells in vitro using recombinant proteins or overexpression of VN and PAI-1 genes, including furin-susceptible (T381) and furin-resistant VN (A381). VN processing was analyzed using a mutant PAI-1 with relatively weaker binding to VN. VN function was evaluated by survival of radiation-damaged endothelial cells. Wild-type, but not mutant PAI-1 inhibited furin-dependent VN processing. Gene transfer revealed that furin-susceptible VN was processed more than the furin-resistant form, but processing of both was inhibited by PAI-1 overexpression. Intracellular PAI-1 formed a complex with VN75 (T381) in cells and media, and the VN75 form was secreted preferentially. Only VN75 protected against radiation-induced endothelial cell death, in which its effect was abolished by wild-type but not mutant PAI-1. These findings indicate that intracellular PAI-1 inhibits VN processing and protects against radiation-induced endothelial cell death. | |||||
書誌情報 |
Vascular Pharmacology 巻 87, p. 150-158, 発行日 2016-12 |
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出版者 | ||||||
出版者 | Elsevier | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.vph.2016.09.006 |