title: Different effects of myotoxins bothropstoxin-I and II from Bothrops snake venom on cation transport ATPases from murine fast twitch skeletal muscle.
abstract: Bothrops jararacussu venom drastically decreases sarcoplasmic Ca(2+)-ATPase (SERCA) protein expression in vivo and inhibits its activity in vitro, in contrast to a slight increase of Na(+)/K(+)-ATPase expression in murine EDL. We investigated the effect of myotoxins bothropstoxin-I and/or -II (BthTX-I, BthTX-II and BthTX-I+II) on this model. No changes were seen in SERCA1, SERCA2 and Na(+)/K(+)-ATPase α1 protein expression as well as (2+)Ca-ATPase activity, but BthTX-II (1 μg/g) reduced Na(+)/K(+)-ATPase α2 expression by 50% one day after perimuscular injection. Interestingly, BthTX-II inhibited Ca(2+)-ATPase activity (IC50 around 6 nM). Our findings suggest that only BthTX-II affects ion transport ATPases, being a potent SERCA inhibitor and a putative target for antivenom drug development.
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ayres
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Priscilla R O
authors.initials: PR
authors.lastname: Feijó
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Adelia C O
authors.initials: AC
authors.lastname: Cintra
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Tomaz
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Valéria M N
authors.initials: VM
authors.lastname: Cunha
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: lquintas@farmaco.ufrj.br.
authors.forename: Luis Eduardo M
authors.initials: LE
authors.lastname: Quintas
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D017837:Bothrops / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003435:Crotalid Venoms / Q000378:metabolism* / Q000633:toxicity; D054501:Group II Phospholipases A2 / Q000633:toxicity*; D020128:Inhibitory Concentration 50; D051379:Mice; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; C078097:bothropstoxin; D054501:Group II Phospholipases A2; C072031:bothropstoxin II; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Bothrops jararacussu myotoxins; Ca(2+)-ATPase; Extensor digitorum longus; Na(+)/K(+)-ATPase; Snake venom