Protein quality control in skeletal muscle weakness/wasting: role of β2-adrenoceptor.

Author(s)

Juliane Cruz Campos

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2017-08-25

Examining board members

Julio Cesar Batista Ferreira; Fabiana de Sant'Anna Evangelista; Emer Suavinho Ferro; William Tadeu Lara Festuccia; Leonardo dos Reis Silveira

• Advisor: Julio Cesar Batista Ferreira

Abstract

The protein quality control (PQC) detects, repairs and disposes cytotoxic proteins through different proteolytic systems (proteasome and autophagy). Here, we characterized the PQC profile as well as the benefits of sustained β2-adrenoceptor activation (β2-AR) a positive PQC modulator, during skeletal muscle atrophy in a rat model of sciatic nerve constriction (SNC). PQC is disrupted in SNC rats, demonstrated by elevated proteasomal and lysosomal activities along with accumulation of cytotoxic proteins and pro-apoptotic factors. The β2-AR activation (Formoterol) promotes a further increase in proteasomal activity, along with autophagic flux reestablishment. Of interest, sustained autophagy inhibition, but not proteasomal inhibition, is sufficient to abolish Formoterol effects on skeletal muscle PQC, mass and strength. These findings suggest a new contribution of β2-AR signalling pathway to the pathophysiology of skeletal muscle where β2-AR restores the impaired PQC, therefore contributing to a better skeletal muscle morphology and function. (AU)

• FAPESP's process: 12/14416-1 - Protein quality control profile in skeletal muscle wasting: role of beta2- adrenergic receptor
• Grantee: Juliane Cruz Campos
• Support Opportunities: Scholarships in Brazil - Doctorate