Textilinins from Pseudonaja textilis textilis. Characterization of two plasmin inhibitors that reduce bleeding in an animal model.
The incidence of vein-graft occlusion associated with myocardial infarction and thrombosis following the use of the plasmin inhibitor, aprotinin, to reduce blood loss during vascular surgery has prompted the isolation of an alternative kinetically distinct inhibitor of plasmin from the venom of Pseudonaja textilis. This inhibitor has been called textilinin (Txln) and two distinct forms have been isolated from the Brown-snake venom (molecular weight, 6688 and 6692). A comparison of plasmin inhibitor constants for aprotinin and the Txlns 1 and 2 indicated that the former bound very tightly (inhibitor constant, Ki approximately 10(-11) mol/l), while both of the latter bound less tightly (Ki approximately 10(-9) mol/l). Homogeneity of Txlns 1 and 2 was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and mass spectrometry. A sequence difference of six amino acids was observed between the two forms of Txln. Txln 1 and 2 showed, respectively, 45 and 43% homology with aprotinin, while there was 58 and 55% homology, respectively, with a plasmin inhibitor from the venom of eastern Taipan, Oxyuranus scutellatus. Both Txlns have six cysteines, like other inhibitors of this group, and homology was determined by alignment of these cysteines. Both have been shown to reduce blood loss by about 60% in a murine tail vein bleeding model. It is proposed that the kinetic profiles of Txln 1 and 2 for plasmin allow the arrest of haemorrhage without the possible threat of thrombosis.
Masci
P P
PP
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia.
Whitaker
A N
AN
Sparrow
L G
LG
de Jersey
J
J
Winzor
D J
DJ
Watters
D J
DJ
Lavin
M F
MF
Gaffney
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D016063:Blood Loss, Surgical / Q000517:prevention & control; D004546:Elapid Venoms / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006470:Hemorrhage / Q000188:drug therapy*; D051379:Mice; D008969:Molecular Sequence Data; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology*
D004546:Elapid Venoms; D015842:Serine Proteinase Inhibitors; C413544:textilinin; D007611:Aprotinin; D005341:Fibrinolysin