Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
Arcaro, Carlos Alberto [1] ; Assis, Renata Pires [1] ; Oliveira, Juliana Oriel [1] ; Zanon, Neusa Maria [2] ; Paula-Gomes, Silvia [3] ; Carvalho Navegantes, Luiz Carlos [2] ; Kettelhut, Isis Carmo [2, 4, 5] ; Brunetti, Iguatemy Lourenco [1] ; Baviera, Amanda Martins [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ Unesp, Sch Pharmaceut Sci, Dept Clin Anal, Rodovia Araraquara Jau, Km 01 S-N, Araraquara, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Sao Paulo - Brazil
[3] Univ Fed Ouro Preto, Dept Biol Sci, Ouro Preto, MG - Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem, Sao Paulo - Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Immunol, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Life Sciences; v. 278, AUG 1 2021.
Citações Web of Science: 0
Resumo

Aim: 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. (AU)

Processo FAPESP: 14/12202-0 - Papel de efetores ativados por AMP cíclico, PKA e EPAC, no controle dos processos proteolíticos dependente de cálcio, mediado por caspase e do sistema ubiquitina-proteassoma na atrofia muscular induzida pelo diabetes
Beneficiário:Carlos Alberto Arcaro Filho
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/18861-2 - Sinalização dependente de EPAC/AKT/FoxO e o controle do processo proteolítico mediado por caspase e do sistema ubiquitina-proteassoma na atrofia muscular induzida pelo diabetes
Beneficiário:Amanda Martins Baviera
Linha de fomento: Auxílio à Pesquisa - Regular