Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Life Science / 生命科學院
  3. Biochemical Sciences / 生化科學研究所
  4. Functional Significance of Two Kunitz-type Protease Inhibitors Isolated from Daboia russelii russelii Snake Venom
 
  • Details

Functional Significance of Two Kunitz-type Protease Inhibitors Isolated from Daboia russelii russelii Snake Venom

Date Issued
2009
Date
2009
Author(s)
Cheng, An-Chun
URI
http://ntur.lib.ntu.edu.tw//handle/246246/178865
Abstract
Snake venoms contain a wide variety of biologically active substances that upset the intricate balance of hemostasis. Many of these proteins have been thoroughly characterized in relation to their functions and applications to molecular and clinical research. However, the functional significance of Kunitz-type protease inhibitors remains obscure. In this study, we purified two Kunitz-type protease inhibitors, namely DrKIn-I and DrKIn-II, from the venom of Daboia russelii russelii (Pakistan), with molecular masses of 7550 and 6940 respectively. APTT, PT, TT and ST tests revealed that both DrKIn-I and DrKIn-II inhibit the intrinsic pathway of coagulation, and tests with single factor deficient plasma showed that this inhibition is mainly through the inactivation of FXII. Amidolytic activity assays revealed that DrKIn-I, compared to DrKIn-II, has higher specificities for FXIIa and FXIa, while DrKIn-II has higher specificities for plasma kallikrein, plasmin and activated protein C. Incubation of DrKIn-I with human plasma decreased the generation of bradykinin in a dose-dependent manner and that this decrease correlates well with increased ADP-induced platelet aggregation and decreased vascular permeability. The pro-aggregatory effect on platelets appears to be mediated through a decrease in intracellular cyclic AMP levels. Furthermore, 7 nM of DrKIn-I almost completely abrogated the activation of protein C by the thrombin-thrombomodulin complex, and that co-injection of RVV-X (the factor X activator in the same venom) and DrKIn-I, but not DrKIn-II, significantly decreased the level of fibrinogen in mice compared to RVV-X alone. DrKIn-II, on the other hand, has less pronounced effect on bradykinin generation and protein C activation. However, treatment of DrKIn-II with the euglobulin fraction significantly prolonged the clot lysis time, compared to DrKIn-I, and that co-administration of RVV-X and DrKIn-II reduced the generation of fibrinogen/fibrin degradation products in mice, confirming the anti-fibrinolytic role of DrKIn-II. We therefore propose that both DrKIn-I and DrKIn-II are prothrombotic agents that help to synergize the procoagulating effects of RVV-X in snakebite symptoms.
Subjects
intrinsic pathway
euglobulin fraction
bradykinin
clot lysis time
File(s)
Loading...
Thumbnail Image
Name

ntu-98-R96b46011-1.pdf

Size

23.32 KB

Format

Adobe PDF

Checksum

(MD5):db70975c1230323a3a64c085c09ba0e5

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science