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The kallikrein-like activity of Heloderma venom is inhibited by carbon monoxide.
- Source :
-
Journal of thrombosis and thrombolysis [J Thromb Thrombolysis] 2019 May; Vol. 47 (4), pp. 533-539. - Publication Year :
- 2019
-
Abstract
- Lizards in the genus Heloderma are the most ancient venomous reptiles, with a traceable lineage nearly 100 million years old. The proteome of the venom of three of the remaining species (Heloderma suspectum, H. exasperatum, H. horridum) are very conserved, with kallikrein-like activity present to cause critical hypotension to immobilize and outright kill prey. Kallikrein-like activity would be expected to activate the contact protein pathway of coagulation, which would be detectable with thrombelastography in human plasma. Thus, it was proposed to determine if kallikrein-like activity could be detected with thrombelastography, and if this activity could be inhibited by carbon monoxide (CO) via a putative heme-based mechanism. Procoagulant activity of each venom was assessed via thrombelastography with normal plasma, and kallikrein-like activity confirmed with FX-depleted plasma. Venom was then exposed to carbon monoxide releasing molecule-2 (CORM-2) or its inactive releasing molecule to assess CO inhibition. All three venoms demonstrated kallikrein-like activity with the same potency and inhibition of activity by CO. In conclusion, the present work documented that procoagulant, kallikrein-like activity containing venoms of the oldest species of venomous reptiles was inhibited by CO, potentially via heme modulation. This is also the first identification and characterization of a kallikrein-like enzyme utilizing coagulation factor-depleted plasma to assess venom that inflicts hypotension. Future investigations will continue to define the vulnerability of venom enzymatic activities to CO.
- Subjects :
- Animals
Humans
Thrombelastography
Blood Coagulation drug effects
Carbon Monoxide chemistry
Kallikreins antagonists & inhibitors
Kallikreins chemistry
Kallikreins pharmacology
Lizards
Reptilian Proteins antagonists & inhibitors
Reptilian Proteins chemistry
Reptilian Proteins pharmacology
Venoms chemistry
Venoms pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-742X
- Volume :
- 47
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and thrombolysis
- Publication Type :
- Academic Journal
- Accession number :
- 30955141
- Full Text :
- https://doi.org/10.1007/s11239-019-01853-6