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PMID:19236611

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Citation

Flight, SM, Johnson, LA, Du, QS, Warner, RL, Trabi, M, Gaffney, PJ, Lavin, MF, de Jersey, J and Masci, PP (2009) Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss. Br. J. Haematol. 145:207-11

Abstract

Aprotinin has been used widely in surgery as an anti-bleeding agent but is associated with a number of side effects. We report that textilinin-1, a serine protease inhibitor from Pseudonaja textilis venom with sequence relatedness to aprotinin, is a potent but reversible plasmin inhibitor and has a narrower range of protease inhibition compared to aprotinin. Like aprotinin, textilinin-1 at 5 micromol/l gave almost complete inhibition of tissue plasminogen activator-induced fibrinolysis of whole blood clots. The activated partial thromboplastin time for plasma was markedly increased by aprotinin but unaffected by textilinin-1. In a mouse tail-vein bleeding model, intravenous textilinin-1 and aprotinin caused similar decreases in blood loss but time to haemostasis in the textilinin-treated animals was significantly shorter than in aprotinin-treated mice. Based on these data, textilinin-1 merits further investigation as a therapeutic alternative to aprotinin.

Links

PubMed Online version:10.1111/j.1365-2141.2009.07605.x

Keywords

Analysis of Variance; Animals; Aprotinin/therapeutic use; Blood Loss, Surgical/prevention & control; Elapid Venoms/therapeutic use; Fibrinolysin/antagonists & inhibitors; Fibrinolysis/drug effects; Hemostasis; Mice; Serine Proteinase Inhibitors/therapeutic use; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

PSETT:VKT1

GO:0004867: serine-type endopeptidase inhibitor activity

ECO:0000314:

F

Table 1: textilinin-1 shows inhibition activity of plasmin and trypsin(low Ki values)

complete
CACAO 6833

PSETT:VKT1

GO:0035899: negative regulation of blood coagulation in other organism

ECO:0000314:

P

Fig. 1D: Textilinin-1 negatively regulated blood loss in a mouse tail vein model

complete
CACAO 6934

PSETT:VKT1

enables

GO:0004867: serine-type endopeptidase inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

PSETT:VKT1

involved_in

GO:0035899: negative regulation of blood coagulation in other organism

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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