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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 187, p. 603-613, SEP 30 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/15107-6 - Role of prostaglandins in the proliferation and differentiation of C2C12 muscle cells, induced by a phospholipase A2 isolated from snake venom
• Grantee: Nadine Cardoso Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/25437-8 - Characterization of the release profile and the regulatory activity of eicosanoids in the degeneration and regeneration of skeletal muscle following injury
• Grantee: Vanessa Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/10937-3 - Satellite cells: effects of lipocalin, hemolin and derived peptides on proliferation and differentiation of quiescent skeletal muscle cells
• Grantee: Angela María Alvarez Gómez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral