Carbon monoxide inhibits the anticoagulant activity of phospholipase A 2 purified from Crotalus adamanteus venom

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9 Scopus citations

Abstract

Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A 2 (PLA 2 ), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA 2 , the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA 2 purified from Crotalus adamanteus venom (Ca-PLA 2 ) in human plasma with thrombelastography and determine if carbon monoxide could inhibit its activity. Coagulation kinetics were determined in human plasma with a range of Ca-PLA 2 activity (0–2 U/ml) via thrombelastography. Then, using carbon monoxide releasing molecule-2 or its inactivated molecule (0 or 100 µM), the vulnerability of Ca-PLA 2 activity to carbon monoxide mediated inhibition was assessed. Lastly, the inhibitory response of Ca-PLA 2 activity to exposure to carbon monoxide releasing molecule-2 (0–100 µM) was determined. Ca-PLA 2 activity degraded the velocity of clot growth and clot strength in an activity dependent, exponential manner. Carbon monoxide inhibited Ca-PLA 2 activity in a concentration dependent fashion, with loss of detectable activity at 100 µM of carbon monoxide releasing molecule-2. These findings, while preliminary, open the possibility that other PLA 2 contained in snake venom with multiple toxicities (e.g., myotoxin, neurotoxin) may be heme bearing and CO-inhibitable, which have profound potential basic and clinical science implications.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalJournal of Thrombosis and Thrombolysis
Volume47
Issue number1
DOIs
StatePublished - Jan 15 2019

Keywords

  • Anticoagulation
  • Carbon monoxide
  • Phospholipase A
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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