Muscle proteolysis via ubiquitin-proteasome system (UPS) is activated by BthTx-I Lys49 PLA(2) but not by BthTx-II Asp49 PLA(2) and Bothrops jararacussu venom

Autor(es)

Kenzo-Kagawa, Bruno ^[1] ; Vieira, Willians Fernando ^{[2, 1]} ; Cogo, Jose Carlos ^[3] ; da Cruz-Hofling, Maria Alice ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Rua Monteiro Lobato 255, BR-13083970 Campinas, SP - Brazil

^[2] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[3] Brazil Univ, Fac Biomed Engn, Itaquera - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicology and Applied Pharmacology; v. 402, SEP 1 2020.
• Citações Web of Science: 0

Resumo

Bites by viperid snakes belonging to Bothrops genus produce fast and intense local edema, inflammation, bleeding and myonecrosis. In this study, we investigated the role of Myogenic Regulatory Factors (MRFs: MyoD; Myog), negatively regulated by GDF-8 (Myostatin), and ubiquitin-proteasome system pathway (UPS: MuRF-1; Fbx-32) in gastrocnemius muscle regeneration after Bothrops jararacussu snake venom (Bjussu) or its isolated phospholipase A(2) myotoxins, BthTx-I (Lys-49 PLA(2)) and BthTx-II (Asp-49 PLA(2)) injection. Male Swiss mice received a single infra-gastrocnemius injection of crude Bjussu, at a dose/volume of 0.83 mg/kg/20 mu l, and BthTx-I or BthTx-II, at a dose/volume of 2.5 mg/kg/20 mu l. Control mice (Sham) received an injection of sterile saline solution (NaCl 0.9%; 20 mu l). At 24, 48, 72 and 96 h post injection, right gastrocnemius was collected for protein expression analyses. Based on the temporal expressional dynamics of MyoD, Myog and GDF-8/Myostatin, it was possible to propose that the myogenesis pathway was impacted most badly by BthTx-II followed by BthTx-I and lastly by B. jararacussu venom, thus suggesting that catalytic activity has likely inhibitory role on the satellite cells-mediated reparative myogenesis pathway. Inversely, the catalytic activity seems to be not a determinant for the activation of proteins ubiquitination by MuRF-1 and Fbx-32/Atrogin-1 E3 proteasome ligases, given proteolysis pathway through UPS was activated neither after Bjussu, nor after BthTx-II, but just after the catalytically-inactive BthTx-I Lys-49 PLA(2)-homologue exposure. The findings of this study disclose interesting perspective for further mechanistic studies about pathways that take part in the atrophy and repair after permanent damage induced by bothropic snakebites. (AU)

• Processo FAPESP: 05/53625-1 - Ação dos mastoparanos e da fosfolipase A2 isolados do veneno de Polybia paulista (Hymenoptera, Epiponini) nos mecanismos de apoptose e necrose de células musculares e mitocôndrias isoladas de camundongos Balb/c
• Beneficiário: Maria Alice da Cruz Hofling
• Modalidade de apoio: Auxílio à Pesquisa - Regular