Thromb Haemost 1981; 45(01): 082-085
DOI: 10.1055/s-0038-1650134
Original Article
Schattauer GmbH Stuttgart

Lack of Correlation between Anticoagulant Activity and Phospholipid Hydrolysis by Snake Venom Phospholipases A2

Eleonora Condrea
+   The Section of Pharmacology and Toxicology, the University of Connecticut, School of Pharmacy, Storrs, CT., USA
,
Chen-Chung Yang
++   Institute of Molecular Biology, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China
,
Philip Rosenberg
+   The Section of Pharmacology and Toxicology, the University of Connecticut, School of Pharmacy, Storrs, CT., USA
› Author Affiliations
Further Information

Publication History

Received 17 July 1980

Accepted 22 December 1980

Publication Date:
24 July 2018 (online)

Summary

The anticoagulant effects and the simultaneous plasma phospholipid hydrolysis induced by three purified phospholipases obtained from snake venoms, i.e., the basic, relatively toxic N. nigricollis, the neutral, relatively nontoxic H. haemachatus, and the acidic, relatively nontoxic N. n. atra, have been compared. The N. nigricollis phospholipase has a very strong anticoagulant effect at concentrations which induce relatively low levels of phospholipid hydrolysis in plasma. The H. haemachatus and N. n. atra phospholipases become anticoagulant only at high concentrations, and the associated phospholipid hydrolysis is also very high. It is concluded that, while all phospholipases are likely to inhibit coagulation if used in amounts sufficiently large to deplete plasma of phospholipids, strongly active phospholipases, such as N. nigricollis, interfere nonenzymatically with the clotting process before any appreciable phospholipid hydrolysis is reached.

 
  • References

  • 1 Boffa MC, Rothen C, Verheij B, Verger R, De Haas G. Enzymatic and anticoagulant activity of phospholipases A2 . Abstracts of the 6th International Symposium on Animal, Plant, and Microbial Toxins. Uppsala August 1979, Toxicon 1979; 17 Suppl 111
  • 2 Condrea E, Yang CC, Rosenberg P. A comparison of a relatively toxic phospholipase A2 from Naja nigricollis snake venom with that of a relatively nontoxic phospholipase A2 from Hemachatus haemachatus snake venom: I. Enzymatic activity on free and membrane bound substrates. Biochem Pharmacol 1980; 29: 1555-1563
  • 3 Condrea E, Fletcher JE, Rapuano B, Yang CC, Rosenberg P. Effect of modification of one histidine residue on the enzymatic and pharmacological properties of a toxic phospholipase A2 from Naja nigricollis venom and less toxic phospholipases A2 from Hemachatus haemachatus and Naja naja atra snake venom. Toxicon. 1980. in press.
  • 4 Fletcher JE, Rapuano B, Condrea E, Yang CC, Rosenberg P. A comparison of a relatively toxic phospholipase A2 from Naja nigricollis snake venom with that of a relatively nontoxic phospholipase A2 from Hemachatus haemachatus snake venom: II. Pharmacological properties in relationship to enzymatic activity. Biochem Pharmacol 1980; 29: 1565-1574
  • 5 Boffa MC, Delori P, Soulier JP. Anticoagulant factors from viperidae venoms. Platelet phospholipid inhibitors. Thrombos Diathes Hemorrh 1972; 28: 509-523
  • 6 Boffa MC, Boffa GA. A phospholipase A2 with anticoagulant activity. II. Inhibition of the phospholipid activity in coagulation. Biochim Biophys Acta 1976; 429: 839-852
  • 7 Prigent-Dachary J, Boffa MC, Boisseau MR, Dufourcq J. Snake venom phospholipases A2 . A fluorescence study of their binding to phospholipid vesicles correlation with their anticoagulant activities. J Biol Chem 1980; 225: 7734-7739
  • 8 Ouyang C, Jy WT, Zan YP, Teng CM. Mechanism of the anticoagulant action of phospholipase A2 purified from Trimeresurus mucrosquamatus snake venom. Toxicon. 1980. in press.
  • 9 Ouyang C, Teng CM, Chen YC, Lin SC. Purification and characterization of the anticoagulant principle of Trimeresurus mucrosquamatus venom. Biochim Biophys Acta 1978; 541: 394-407
  • 10 Evans HJ, Franson R, Qureshi GD, Moo-Penn WF. Isolation of anticoagulant proteins from cobra venom (Naja nigricollis). Identity with phospholipases A2 . J Biol Chem 1980; 255: 3793-3797
  • 11 Yang CC, King K. Chemical modification of the histidine residue in basic phospholipase A2 from the venom of Naja nigricollis. Biochim Biophys Acta 1980; 614: 373-388
  • 12 Joubert FJ. Hemachatus haemachatus (Ringhals) venom. Purification, some properties and amino acid sequence of phospholipase A (fraction DE-1). Eur J Biochem 1975; 52: 539-545
  • 13 Yang CC, King K. Chemical modification of the histidine residue in phospholipase A2 from the venom of Hemachatus haemachatus. Toxicon. 1980. in press.
  • 14 Yang CC, King K, Sun TP. Chemical modification of lysine and histidine residues in phospholipase A2 from the venom of Naja naja atra. Toxicon. 1981. in press.
  • 15 Marinetti GB, Albrecht M, Ford T, Stotz E. Analysis of human plasma phosphatides by paper chromatography. Biochim Biophys Acta 1959; 36: 04-13
  • 16 Folch J, Lees M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 1957; 226: 497-509
  • 17 Condrea E, Rosenberg P, Dettbam WD. Demonstration of phospholipid splitting as the factor responsible for increased permeability and block of axonal conduction induced by snake venom. I. Study on lobster axons. Biochim Biophys Acta 1967; 135: 669-681
  • 18 Bartlett GR. Phosphorous assay in column chromatography. J Biol Chem 1959; 234: 466-468
  • 19 Biology data book. Altman PL, Dittmer DS. (ed) FASEB, Bethesda; Maryland: 1974. Vol 03. p 1817
  • 20 Zwaal RF A. Membrane and lipid involvement in blood coagulation. Biochim Biophys Acta 1978; 515: 163-205
  • 21 Condrea E, de Vries A, Mager J. Action of snake venom phospholipase A on free and lipoprotein-bound phospholipids. Biochim Biophys Acta 1962; 58: 389-397