Myotoxic phospholipases A2 isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells
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Abstract
This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A2 (PLA2s) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing Mr ∼ 14,000 for the monomer and 28,000 Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA2s from snake venoms, MTX-I belonging to Asp49 PLA2 class, enzymatically active, and MTX-II to Lys49 PLA2s, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA2 and anticoagulant activities, corroborating the importance of residue His48 and Ca2+ ions for the enzymatic catalysis. Both PLA2s induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA2 proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer. © 2008 Elsevier Inc. All rights reserved.
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Bothrops brazili , Cytotoxicity , Microbicide , Myotoxins , Phospholipases A2 , Snake venom , Synthetic peptides , dimer , edetic acid , histidine , lysine , monomer , myotoxin 1 , myotoxin 2 , phospholipase A2 , sepharose , snake venom , synthetic peptide , unclassified drug , amino terminal sequence , animal experiment , animal model , anticoagulation , antimicrobial activity , Candida albicans , carboxy terminal sequence , catalysis , controlled study , cytotoxicity , edema , enzyme activity , Escherichia coli , human , human cell , Leishmania , male , mouse , nonhuman , priority journal , snake , T cell leukemia , Amino Acid Sequence , Animals , Bothrops , Cell Line, Tumor , Crotalid Venoms , Humans , Isoenzymes , Male , Mice , Microbial Sensitivity Tests , Molecular Sequence Data , Peptide Mapping , Peptides , Sequence Alignment , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Crotalus , Leishmania sp.
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English
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Peptides, v. 29, n. 10, p. 1645-1656, 2008.
