Carbon monoxide inhibits the anticoagulant activity of phospholipase A2 purified from Crotalus adamanteus venom

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3 Citations (Scopus)

Abstract

Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A2 (PLA2), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA2, the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA2 purified from Crotalus adamanteus venom (Ca-PLA2) 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-PLA2 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-PLA2 activity to carbon monoxide mediated inhibition was assessed. Lastly, the inhibitory response of Ca-PLA2 activity to exposure to carbon monoxide releasing molecule-2 (0–100 µM) was determined. Ca-PLA2 activity degraded the velocity of clot growth and clot strength in an activity dependent, exponential manner. Carbon monoxide inhibited Ca-PLA2 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 PLA2 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)
JournalJournal of Thrombosis and Thrombolysis
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Crotalus
Phospholipases A2
Venoms
Carbon Monoxide
Anticoagulants
Thrombelastography
Snake Venoms
Neurotoxins
Heme

Keywords

  • Anticoagulation
  • Carbon monoxide
  • Phospholipase A
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Carbon monoxide inhibits the anticoagulant activity of phospholipase A2 purified from Crotalus adamanteus venom",
abstract = "Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A2 (PLA2), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA2, the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA2 purified from Crotalus adamanteus venom (Ca-PLA2) 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-PLA2 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-PLA2 activity to carbon monoxide mediated inhibition was assessed. Lastly, the inhibitory response of Ca-PLA2 activity to exposure to carbon monoxide releasing molecule-2 (0–100 µM) was determined. Ca-PLA2 activity degraded the velocity of clot growth and clot strength in an activity dependent, exponential manner. Carbon monoxide inhibited Ca-PLA2 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 PLA2 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.",
keywords = "Anticoagulation, Carbon monoxide, Phospholipase A, Thrombelastography",
author = "Nielsen, {Vance G}",
year = "2018",
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doi = "10.1007/s11239-018-1763-6",
language = "English (US)",
journal = "Journal of Thrombosis and Thrombolysis",
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AU - Nielsen, Vance G

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N2 - Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A2 (PLA2), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA2, the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA2 purified from Crotalus adamanteus venom (Ca-PLA2) 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-PLA2 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-PLA2 activity to carbon monoxide mediated inhibition was assessed. Lastly, the inhibitory response of Ca-PLA2 activity to exposure to carbon monoxide releasing molecule-2 (0–100 µM) was determined. Ca-PLA2 activity degraded the velocity of clot growth and clot strength in an activity dependent, exponential manner. Carbon monoxide inhibited Ca-PLA2 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 PLA2 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.

AB - Snake venom contains a myriad of classes of enzyme which have been investigated for medicinal and toxinological purposes, including phospholipase A2 (PLA2), which is responsible for anticoagulant, myotoxic and neurotoxic effects. Given the importance of PLA2, the purposes of the present investigation were to characterize the coagulation kinetic behavior of a PLA2 purified from Crotalus adamanteus venom (Ca-PLA2) 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-PLA2 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-PLA2 activity to carbon monoxide mediated inhibition was assessed. Lastly, the inhibitory response of Ca-PLA2 activity to exposure to carbon monoxide releasing molecule-2 (0–100 µM) was determined. Ca-PLA2 activity degraded the velocity of clot growth and clot strength in an activity dependent, exponential manner. Carbon monoxide inhibited Ca-PLA2 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 PLA2 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.

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