Antifibrinolytic Role of a Bee Venom Serine Protease Inhibitor That Acts as a Plasmin Inhibitor

被引:68
作者
Choo, Young Moo [1 ]
Lee, Kwang Sik [1 ]
Yoon, Hyung Joo [2 ]
Qiu, Yuling [1 ]
Wan, Hu [1 ]
Sohn, Mi Ri [1 ]
Sohn, Hung Dae [1 ]
Jin, Byung Rae [1 ]
机构
[1] Dong A Univ, Coll Nat Resources & Life Sci, Pusan, South Korea
[2] Natl Acad Agr Sci, Dept Agr Biol, Suwon, South Korea
关键词
PSEUDONAJA-TEXTILIS; BLOOD-COAGULATION; APROTININ; EVOLUTION; PURIFICATION; HEMOSTASIS; ENZYME;
D O I
10.1371/journal.pone.0032269
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bee venom is a rich source of pharmacologically active substances. In this study, we identified a bumblebee (Bombus ignitus) venom Kunitz-type serine protease inhibitor (Bi-KTI) that acts as a plasmin inhibitor. Bi-KTI showed no detectable inhibitory effect on factor Xa, thrombin, or tissue plasminogen activator. In contrast, Bi-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent; however, this inhibitory ability was two-fold weaker than that of aprotinin. The fibrin(ogen)olytic activities of B. ignitus venom serine protease (Bi-VSP) and plasmin in the presence of Bi-KTI indicate that Bi-KTI targets plasmin more specifically than Bi-VSP. These findings demonstrate a novel mechanism by which bumblebee venom affects the hemostatic system through the antifibrinolytic activity of Bi-KTI and through Bi-VSP-mediated fibrin(ogen) olytic activities, raising interest in Bi-KTI and Bi-VSP as potential clinical agents.
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页数:5
相关论文
共 25 条
[1]   Snake venom proteins acting on hemostasis [J].
Braud, S ;
Bon, C ;
Wisner, A .
BIOCHIMIE, 2000, 82 (9-10) :851-859
[2]   Molecular cloning and antimicrobial activity of bombolitin, a component of bumblebee Bombus ignitus venom [J].
Choo, Young Moo ;
Lee, Kwang Sik ;
Yoon, Hyung Joo ;
Je, Yeon Ho ;
Lee, Seon Woo ;
Sohn, Hung Dae ;
Jin, Byung Rae .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 2010, 156 (03) :168-173
[3]   Dual Function of a Bee Venom Serine Protease: Prophenoloxidase-Activating Factor in Arthropods and Fibrin(ogen)olytic Enzyme in Mammals [J].
Choo, Young Moo ;
Lee, Kwang Sik ;
Yoon, Hyung Joo ;
Kim, Bo Yeon ;
Sohn, Mi Ri ;
Roh, Jong Yul ;
Je, Yeon Ho ;
Kim, Nam Jung ;
Kim, Iksoo ;
Woo, Soo Dong ;
Sohn, Hung Dae ;
Jin, Byung Rae .
PLOS ONE, 2010, 5 (05)
[4]   APROTININ - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACY IN REDUCING BLOOD-LOSS ASSOCIATED WITH CARDIAC-SURGERY [J].
DAVIS, R ;
WHITTINGTON, R .
DRUGS, 1995, 49 (06) :954-983
[5]   Comparison of textilinin-1 with aprotinin as serine protease inhibitors and as antifibrinolytic agents [J].
Flight, Simone ;
Johnson, Lambro ;
Trabi, Manuela ;
Gaffney, Patrick ;
Lavin, Martin ;
de Jersey, John ;
Masci, Paul .
PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS, 2005, 34 (4-5) :188-193
[6]   Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss [J].
Flight, Simone M. ;
Johnson, Lambro A. ;
Du, Qianyun S. ;
Warner, Roscoe L. ;
Trabi, Manuela ;
Gaffney, Patrick J. ;
Lavin, Martin F. ;
de Jersey, John ;
Masci, Paul P. .
BRITISH JOURNAL OF HAEMATOLOGY, 2009, 145 (02) :207-211
[7]   Identification and characterization of Harobin, a novel fibrino(geno)lytic serine protease from a sea snake (Lapemis hardwickii) [J].
He, Junyun ;
Chen, Shiyong ;
Gu, Jun .
FEBS LETTERS, 2007, 581 (16) :2965-2973
[8]   HONEYBEE VENOM - A RICH SOURCE OF PHARMACOLOGICALLY ACTIVE PEPTIDES [J].
HIDER, RC .
ENDEAVOUR, 1988, 12 (02) :60-65
[9]   Serine proteases affecting blood coagulation and fibrinolysis from snake venoms [J].
Kini, R. Manjunatha .
PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS, 2005, 34 (4-5) :200-204
[10]   Biochemical characterization of a thrombin-like enzyme and a fibrinolytic serine protease from snake (Agkistrodon saxatilis) venom [J].
Koh, YS ;
Chung, KH ;
Kim, DS .
TOXICON, 2001, 39 (04) :555-560