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Muscle proteolysis via ubiquitin-proteasome system (UPS) is activated by BthTx-I Lys49 PLA2 but not by BthTx-II Asp49 PLA2 and Bothrops jararacussu venom.
Kenzo-Kagawa, Bruno; Vieira, Willians Fernando; Cogo, José Carlos; da Cruz-Höfling, Maria Alice.
Afiliação
  • Kenzo-Kagawa B; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
  • Vieira WF; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP, Brazil; Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP, Brazil.
  • Cogo JC; Faculty of Biomedical Engineering, Brazil University, Itaquera, Brazil.
  • da Cruz-Höfling MA; Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, SP, Brazil. Electronic address: hofling@unicamp.br.
Toxicol Appl Pharmacol ; 402: 115119, 2020 09 01.
Article em En | MEDLINE | ID: mdl-32619552
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 A2 myotoxins, BthTx-I (Lys-49 PLA2) and BthTx-II (Asp-49 PLA2) injection. Male Swiss mice received a single intra-gastrocnemius injection of crude Bjussu, at a dose/volume of 0.83 mg/kg/20 µl, and BthTx-I or BthTx-II, at a dose/volume of 2.5 mg/kg/20 µl. Control mice (Sham) received an injection of sterile saline solution (NaCl 0.9%; 20 µl). 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 PLA2-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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Músculo Esquelético / Venenos de Crotalídeos / Fosfolipases A2 do Grupo II / Proteínas Musculares Limite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Músculo Esquelético / Venenos de Crotalídeos / Fosfolipases A2 do Grupo II / Proteínas Musculares Limite: Animals Idioma: En Revista: Toxicol Appl Pharmacol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos