Back to Search
Start Over
The anticoagulant effect of Apis mellifera phospholipase A 2 is inhibited by CORM-2 via a carbon monoxide-independent mechanism.
- Source :
-
Journal of thrombosis and thrombolysis [J Thromb Thrombolysis] 2020 Jan; Vol. 49 (1), pp. 100-107. - Publication Year :
- 2020
-
Abstract
- Bee venom phospholipase A <subscript>2</subscript> (PLA <subscript>2</subscript> ) has potential for significant morbidity. Ruthenium (Ru)-based carbon monoxide releasing molecules (CORM) inhibit snake venoms that are anticoagulant and contain PLA <subscript>2</subscript> . In addition to modulating heme-bearing proteins with carbon monoxide, these CORM generate reactive Ru species that form adducts with histamine residues resulting in changes in protein function. This study sought to identify anticoagulant properties of bee venom PLA <subscript>2</subscript> via catalysis of plasma phospholipids required for thrombin generation. Another goal was to determine if Ru-based CORM inhibit bee venom PLA <subscript>2</subscript> via carbon monoxide release or via potential binding of reactive Ru species to a key histidine residue in the catalytic site of the enzyme. Anticoagulant activity of bee venom PLA <subscript>2</subscript> was assessed via thrombelastography with normal plasma. Bee venom PLA <subscript>2</subscript> was then exposed to different CORM and a metheme forming agent and anticoagulant activity was reassessed. Using Ru, boron and manganese-based CORM and a metheme forming agent, it was demonstrated that it was unlikely that carbon monoxide interaction with a heme group attached to PLA <subscript>2</subscript> was responsible for inhibition of anticoagulant activity by Ru-based CORM. Exposure of PLA <subscript>2</subscript> to a Ru-based CORM in the presence of histidine-rich human albumin resulted in loss of inhibition of PLA <subscript>2</subscript> . Ru-based CORM likely inhibit bee venom PLA <subscript>2</subscript> anticoagulant activity via formation of reactive Ru species that bind to histidine residues of the enzyme.
- Subjects :
- Animals
Humans
Phospholipase A2 Inhibitors
Anticoagulants chemistry
Bee Venoms antagonists & inhibitors
Bee Venoms chemistry
Bees enzymology
Carbon Monoxide chemistry
Insect Proteins antagonists & inhibitors
Insect Proteins chemistry
Organometallic Compounds chemistry
Phospholipases A2 chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1573-742X
- Volume :
- 49
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and thrombolysis
- Publication Type :
- Academic Journal
- Accession number :
- 31679116
- Full Text :
- https://doi.org/10.1007/s11239-019-01980-0