Neurotoxic, Myotoxic and Cytolytic Activities of the New Basic PLA(2) Isoforms BmjeTX-I and BmjeTX-II Isolated from the Bothrops marajoensis (Maraj Lancehead) Snake Venom

Autor(es)

Ponce-Soto, L. A. ^{[1, 2]} ; Martins-de-Souza, D. ^{[3, 1]} ; Marangoni, S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, State Univ Campinas, Dept Biochem, Inst Biol, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, State Univ Campinas, Dept Pharmacol, Fac Med Sci, BR-13083970 Campinas, SP - Brazil

^[3] Max Planck Inst Psychiat, D-80804 Munich - Germany

• Tipo de documento: Artigo Científico
• Fonte: The Protein Journal; v. 29, n. 2, p. 103-113, FEB 2010.
• Citações Web of Science: 14

Resumo

The BmjeTX-I and BmjeTX-II isoforms of PLA(2) were purified from Bothrops marajoensis venom by ion-exchange chromatography and reverse phase HPLC. Both isoforms showed a molecular mass of 13808.89 Da (BmjeTX-I) and 13863.97 Da (BmjeTX-II) determined by based on the determined primary structures and SDS-PAGE and confirmed experimentally by MALDI-TOF mass spectrometry. Multiple alignment of BmjeTX-I and BmjeTX-II isoforms of PLA(2) show high degree of homology with basic PLA(2) myotoxins from other Bothrops venoms. Ex vivo, both isoforms caused a blockade of the neuromuscular transmission in young chick biventer cervicis preparations in a similar way to other Bothrops species. In chick preparations, contractures to exogenous acetylcholine (55 and 110 mu M) or KCl (13.4 mM) were unaltered after complete blockade for the both isoforms BmjeTX-I and BmjeTX-II of PLA(2). These results, which strongly suggested a presynaptic mechanism of action for these toxins. In mice, both isoforms induced myonecrosis and a systemic interleukin-6 response upon intramuscular injection. Both isoforms BmjeTX-I and BmjeTX-II of PLA(2) also induced moderate marked paw edema, evidencing the local increase in vascular permeability. Since both isoforms of PLA(2) exert a strong proinflammatory effect, the enzymatic hydrolysis of phospholipids might be relevant for this phenomenon and produced cytotoxicity in murine skeletal muscle C2C12 myoblasts and myotubes. (AU)

• Processo FAPESP: 06/51566-0 - Caracterização molecular e funcional de toxinas crotálicas, botrópicas e escorpiônicas: avaliação de suas atividades farmacológicas
• Beneficiário: Luis Alberto Ponce Soto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado