Catalytically active phospholipase A(2) myotoxin from Crotalus durissus terrificus induces proliferation and differentiation of myoblasts dependent on prostaglandins produced by both COX-1 and COX-2 pathways

Autor(es)

Silva, Nadine C. ^[1] ; Alvarez, Angela M. ^{[1, 2]} ; DeOcesano-Pereira, Carlos ^[2] ; Fortes-Dias, Consuelo L. ^[3] ; Moreira, Vanessa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Pharmacol Dept, BR-04044020 Sao Paulo, SP - Brazil

^[2] Butantan Inst, CENTD, BR-05503900 Sao Paulo, SP - Brazil

^[3] Fundacao Ezequiel Dias FUNED, BR-30510010 Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 187, p. 603-613, SEP 30 2021.
• Citações Web of Science: 0

Resumo

Although crotoxin B (CB) is a well-established catalytically active secretory phospholipase A(2) group IIA (sPLA(2)-IIA) myotoxin, we investigated its potential stimulatory effect on myogenesis with the involvement of prostaglandins (PGs) produced by cyclooxygenase (COX)-1 and -2 pathways. Myoblast C2C12 were cultured in proliferation or commitment protocols and incubated with CB followed by lumiracoxib (selective COX-2 inhibitor) or valeryl salicylate (selective COX-1 inhibitor) and subjected to analysis of PG release, cell proliferation and activation of myogenic regulatory factors (MRFs). Our data showed that CB in non-cytotoxic concentrations induces an increase of COX-2 protein expression and stimulates the activity of both COX isoforms to produce PGE(2), PGD(2) and 15d-PGJ(2). CB induced an increase in the proliferation of C2C12 myoblast cells dependent on PGs from both COX-1 and COX-2 pathways. In addition, CB stimulated the activity of Pax7, MyoD, Myf5 and myogenin in proliferated cells. Otherwise, CB increased myogenin activity but not MyoD in committed cells. Our findings evidence the role of COX-1- and COX-2-derived PGs in modulating CB-induced activation of MRFs. This study contributes to the knowledge that CB promote early myogenic events via regulatory mechanisms on PG-dependent COX pathways, showing new concepts about the effect of sPLA(2)-IIA in skeletal muscle repair. (AU)

• Processo FAPESP: 17/15107-6 - Papel de prostaglandinas na proliferação e diferenciação de células musculares C2C12, induzidas por uma fosfolipase A2 isolada do veneno de serpente
• Beneficiário: Nadine Cardoso Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/25437-8 - Caracterização do perfil de liberação e atividade regulatória de eicosanoides na degeneração e regeneração do músculo esquelético, após injúria
• Beneficiário: Vanessa Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/10937-3 - Cálulas satélite: efeitos da lipocalina, hemolina e peptídeos derivados, na proliferação e diferenciação de células quiescentes de músculo esquelético
• Beneficiário: Angela María Alvarez Gómez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado