Phosphodiesterase 4 inhibition restrains muscle proteolysis in diabetic rats by activating PKA and EPAC/Akt effectors and inhibiting FoxO factors

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Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorFederal University of Ouro Preto-
Autor(es): dc.creatorArcaro, Carlos Alberto [UNESP]-
Autor(es): dc.creatorAssis, Renata Pires [UNESP]-
Autor(es): dc.creatorOliveira, Juliana Oriel [UNESP]-
Autor(es): dc.creatorZanon, Neusa Maria-
Autor(es): dc.creatorPaula-Gomes, Silvia-
Autor(es): dc.creatorNavegantes, Luiz Carlos Carvalho-
Autor(es): dc.creatorKettelhut, Isis Carmo-
Autor(es): dc.creatorBrunetti, Iguatemy Lourenço [UNESP]-
Autor(es): dc.creatorBaviera, Amanda Martins [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:50:59Z-
Data de disponibilização: dc.date.available2022-02-22T00:50:59Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.lfs.2021.119563-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/207659-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/207659-
Descrição: dc.descriptionAim: There is growing evidence about the ability of cyclic adenosine monophosphate (cAMP) signaling and nonselective phosphodiesterase (PDE) inhibitors on mitigate muscle atrophy. PDE4 accounts for the major cAMP hydrolyzing activity in skeletal muscles, therefore advances are necessary about the consequences of treatment with PDE4 inhibitors on protein breakdown in atrophied muscles. We postulated that rolipram (selective PDE4 inhibitor) may activate cAMP downstream effectors, inhibiting proteolytic systems in skeletal muscles of diabetic rats. Main methods: Streptozotocin-induced diabetic rats were treated with 2 mg/kg rolipram for 3 days. Changes in the levels of components belonging to the proteolytic machineries in soleus and extensor digitorum longus (EDL) muscles were investigated, as well as cAMP effectors. Key findings: Treatment of diabetic rats with rolipram decreased the levels of atrogin-1 and MuRF-1 in soleus and EDL, and reduced the activities of calpains and caspase-3; these findings partially explains the low ubiquitin conjugates levels and the decreased proteasome activity. The inhibition of muscle proteolysis may be occurring due to phosphorylation and inhibition of forkhead box O (FoxO) factors, probably as a consequence of the increased cAMP levels, followed by the activation of PKA and Akt effectors. Akt activation may be associated with the increased levels of exchange protein directly activated by cAMP (EPAC). As a result, rolipram treatment spared muscle mass in diabetic rats. Significance: The antiproteolytic responses associated with PDE4 inhibition may be helpful to motivate future investigations about the repositioning of PDE4 inhibitors for the treatment of muscle wasting conditions.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionSão Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Clinical Analysis-
Descrição: dc.descriptionDepartment of Physiology Ribeirão Preto Medical School University of São Paulo-
Descrição: dc.descriptionDepartment of Biological Sciences Federal University of Ouro Preto-
Descrição: dc.descriptionDepartments of Biochemistry and Immunology Ribeirão Preto Medical School University of São Paulo-
Descrição: dc.descriptionSão Paulo State University (Unesp) School of Pharmaceutical Sciences Department of Clinical Analysis-
Descrição: dc.descriptionCNPq: 479817/2013-8-
Idioma: dc.languageen-
Relação: dc.relationLife Sciences-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDiabetes mellitus-
Palavras-chave: dc.subjectProteolysis-
Palavras-chave: dc.subjectRolipram-
Palavras-chave: dc.subjectSkeletal muscle-
Palavras-chave: dc.subjectUbiquitin-proteasome system-
Título: dc.titlePhosphodiesterase 4 inhibition restrains muscle proteolysis in diabetic rats by activating PKA and EPAC/Akt effectors and inhibiting FoxO factors-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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