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Toxicon ; 115: 13-21, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26927324

RESUMO

Snake venom is a complex mixture of active compounds consisting of 80-90% proteins and peptides that exhibit a variety of biological actions that are not completely clarified or identified. Of these, phospholipase A2 is one of the molecules that has shown great biotechnological potential. The objectives of this study were to isolate, biochemically and biologically characterize a Lys49 phospholipase A2 homologue from the venom of Bothrops neuwiedi urutu. The protein was purified after two chromatographic steps, anion exchange and reverse phase. The purity and relative molecular mass were assessed by SDS-PAGE, observing a molecular weight typical of PLA2s, subsequently confirmed by mass spectrometry obtaining a mass of 13,733 Da. As for phospholipase activity, the PLA2 proved to be enzymatically inactive. The analyses by Edman degradation and sequencing of the peptide fragments allowed for the identification of 108 amino acid residues; this sequence showed high identity with other phospholipases A2 from Bothrops snake venoms, and identified this molecule as a novel PLA2 isoform from B. neuwiedi urutu venom, called BnuTX-I. In murine models, both BnuTX-I as well as the venom induced edema and myotoxic responses. The cytotoxic effect of BnuTX-I in murine macrophages was observed at concentrations above 12 µg/mL. BnuTX-I also presented antimicrobial activity against gram-positive and negative bacterial strains, having the greatest inhibitory effect on Pseudomonas aeruginosa. The results allowed for the identification of a new myotoxin isoform with PLA2 structure with promising biotechnological applications.


Assuntos
Antibacterianos/farmacologia , Bothrops/metabolismo , Venenos de Crotalídeos/química , Fosfolipases A2/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Venenos de Crotalídeos/isolamento & purificação , Venenos de Crotalídeos/farmacologia , Edema/sangue , Edema/induzido quimicamente , Edema/patologia , Eletroforese em Gel de Poliacrilamida , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Interleucina-1beta/sangue , Masculino , Camundongos , Fosfolipases A2/química , Conformação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Alinhamento de Sequência , Fator de Necrose Tumoral alfa/sangue
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