Carbon monoxide releasing molecule-2 inhibition of snake venom thrombin-like activity: novel biochemical “brake”?

Vance G Nielsen, Charles M. Bazzell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

A complication of defibrinogenation therapy with snake venom enzymes such as ancrod is hypofibrinogenemia associated bleeding secondary to no human-derived inhibitor being available to inactivate or diminish the activity of such enzymes. Of interest, ancrod contains a critical histidine residue without which enzymatic activity is inhibited, and carbon monoxide has been demonstrated to inhibit biomolecular function by interacting with histidine moieties in ion channels. We tested the hypothesis that exposure of three different snake venoms containing serine proteases with thrombin-like activity (which included ancrod) to carbon monoxide derived from carbon monoxide releasing molecule-2 would diminish their effects on plasmatic coagulation as assessed by thrombelastography. In the case of the Malayan pit viper and Eastern diamondback rattlesnake venoms, carbon monoxide diminished the effects of thrombin-like activity. In contrast, timber rattlesnake venom demonstrated enhancement of “thrombin-generating” activity with simultaneous loss of thrombin-like activity in response to carbon monoxide exposure. These findings may serve as the rational basis for not just continuing to investigate the potential of snake venom enzymes as clinical defibrinogenating agents, but to also to assess the potential to stop such agents from becoming a catalytic “runaway train” by judicious application of a biochemical “brake” such as carbon monoxide.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
Volume43
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

  • Carbon monoxide
  • Fibrinogen depleting agent
  • Histidine
  • Snake venom serine protease
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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