BE-I-PLA2, a novel acidic phospholipase A(2) from Bothrops erythromelas venom: Isolation, cloning and characterization as potent anti-platelet and inductor of prostaglandin I-2 release by endothelial cells

BE-I-PLA2, a novel acidic phospholipase A(2) from Bothrops erythromelas venom: Isolation, cloning and characterization as potent anti-platelet and inductor of prostaglandin I-2 release by endothelial cells

Author Albuquerque Modesto, Jeanne Claine de Google Scholar
Spencer, Patrick J. Google Scholar
Fritzen, Marcio Google Scholar
Valenca, Renata C. Google Scholar
Oliva, Maria Luiza Vilela Autor UNIFESP Google Scholar
Bezerra da Silva, Marcia Google Scholar
Chudzinski-Tavassi, Ana Marisa Google Scholar
Camargo Guarnieri, Miriam Google Scholar
Institution Universidade Federal de Pernambuco (UFPE)
Inst Butantan
IPEN
Universidade Federal de São Paulo (UNIFESP)
Abstract A novel acidic Asp49 phospholipase A(2) 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 A(2) 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 I-2, 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. (c) 2006 Elsevier Inc. All rights reserved.
Keywords phospholipase A(2)
snake venoms
platelet
platelet receptors
endothelial cells
prostaglandin I-2
nitric oxide
Language English
Date 2006-07-28
Published in Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 72, n. 3, p. 377-384, 2006.
ISSN 0006-2952 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 377-384
Origin http://dx.doi.org/10.1016/j.bcp.2006.04.032
Access rights Closed access
Type Article
Web of Science ID WOS:000239235000010
URI http://repositorio.unifesp.br/handle/11600/29052

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account