BE-I-PLA2, a novel acidic phospholipase Asub(2) from Bothrops erythromelas venom: isolation, cloning and characterization as potent anti-platelet and inductor of prostaglandin Isub(2) release by endothelial cells
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Biochemical Pharmacology
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A novel acidic Asp49 phospholipase A2 was isolated from Bothrops erythromelas (jararaca malha-de-cascavel) snake venom by four chromatographic steps. BE-I-PLA2 present a molecular weight of 13,649.57 Da as estimated by mass spectrometry. N-terminal and four internal peptides were sequenced, covering around one-third of the complete toxin sequence. The complete BE-I-PLA2 cDNA was cloned from a B. erythromelas venom-gland cDNA library. The cDNA sequence possesses 457 bp and encodes a protein with significant sequence similarity to many other phospholipase A2 from snake venoms. When tested in platelet rich plasma, the enzyme showed a potent inhibitory effect on aggregation induced by arachidonic acid and collagen, but not ADP. On the other hand, BE-I-PLA2 did not modify aggregation in washed platelet. Furthermore, no action of BE-I-PLA2 on the principal platelets receptors was observed. Chemical modification with p-bromophenacyl bromide abolished the enzymatic activity of BE-I-PLA2, but its anti-platelet activity was only partially inhibited. In human umbilical-cord veins endothelial cells, BE-I-PLA2 was neither apoptotic nor proliferative but stimulated endothelial cells to release prostaglandin I2, suggesting an increase of its potential anti-platelet activity in vivo. Further studies are required in order to determine the exact mechanism of action of BE-I-PLA2 in the inhibition of platelet aggregation.
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MODESTO, J.C. de A.; SPENCER, PATRICK J.; FRITZEN, MARCIO; VALENCA, RENATA C.; OLIVA, MARIA L.V.; SILVA, MARCIA B. da; TAVASSI, ANA M.C.; GUARNIERI, MIRIAM C. BE-I-PLA2, a novel acidic phospholipase Asub(2) from Bothrops erythromelas venom: isolation, cloning and characterization as potent anti-platelet and inductor of prostaglandin Isub(2) release by endothelial cells. Biochemical Pharmacology, v. 72, n. 3, p. p. 377-384, 2006. DOI: 10.1016/j.bcp.2006.04.032. Disponível em: http://repositorio.ipen.br/handle/123456789/5403. Acesso em: 20 Mar 2026.
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