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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance

http://hdl.handle.net/2237/25600
9d077061-a5b3-4f2e-8744-3c7431d31945
名前 / ファイル ライセンス アクション
PT596Mut_YT.pdf PT596Mut_YT.pdf ファイル公開:2017/12/01 (615.5 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2017-02-17
タイトル
タイトル Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance
著者 Takagi, Y.

× Takagi, Y.

WEKO 69407

Takagi, Y.

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Murata, M.

× Murata, M.

WEKO 69408

Murata, M.

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Kozuka, T.

× Kozuka, T.

WEKO 69409

Kozuka, T.

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Nakata, Y.

× Nakata, Y.

WEKO 69410

Nakata, Y.

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Hasebe, R.

× Hasebe, R.

WEKO 69411

Hasebe, R.

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Tamura, S.

× Tamura, S.

WEKO 69412

Tamura, S.

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Takagi, A.

× Takagi, A.

WEKO 69413

Takagi, A.

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Matsushita, T.

× Matsushita, T.

WEKO 69414

Matsushita, T.

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Saito, H.

× Saito, H.

WEKO 69415

Saito, H.

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Kojima, T.

× Kojima, T.

WEKO 69416

Kojima, T.

Search repository
権利
権利情報 “This article is not an exact copy of the original published article in (Thrombosis and Haemostasis). The definitive publisher-authenticated version of (Takagi Y, Murata M, Kozuka T, Nakata Y, Hasebe R, Tamura S, Takagi A, Matsushita T, Saito H, Kojima T; Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance, Thrombosis and Haemostasis. v.116, n.6, 2016, p.1003-1181 ) is available online at: (https://doi.org/10.1160/TH16-03-0223).“
キーワード
主題Scheme Other
主題 prothrombin
キーワード
主題Scheme Other
主題 missense variant
キーワード
主題Scheme Other
主題 Arg596
キーワード
主題Scheme Other
主題 antithrombin resistance
キーワード
主題Scheme Other
主題 thrombomodulin resistance
抄録
内容記述 Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0 %, in contrast to values of all variants were maintained at above 80 %. The thrombin–AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12 %, whereas that of tested variants was 37 %–56 %. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin–TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin–TM affinity-dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM-mediated anticoagulation.
内容記述タイプ Abstract
出版者
出版者 Schattauer Publishers
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
ISSN
収録物識別子タイプ ISSN
収録物識別子 0340-6245
書誌情報 Thrombosis and Haemostasis

巻 116, 号 6, p. 1003-1181, 発行日 2016-12
著者版フラグ
値 author
URI
識別子 https://doi.org/10.1160/TH16-03-0223
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/25600
識別子タイプ HDL
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