Exercise Training Attenuates Ubiquitin-Proteasome Pathway and Increases the Genes Related to Autophagy on the Skeletal Muscle of Patients With Inflammatory Myopathies

Isabela Bruna Pires Borges; Diego Sales de Oliveira; Suely Kazue Nagahashi Marie; Antonio Marcondes Lenario; Sueli Mieko Oba-Shinjo; Samuel Katsuyuki Shinjo

doi:10.1097/RHU.0000000000001721

Exercise Training Attenuates Ubiquitin-Proteasome Pathway and Increases the Genes Related to Autophagy on the Skeletal Muscle of Patients With Inflammatory Myopathies

J Clin Rheumatol. 2021 Sep 1;27(6S):S224-S231. doi: 10.1097/RHU.0000000000001721.

Authors

Isabela Bruna Pires Borges¹, Diego Sales de Oliveira¹, Suely Kazue Nagahashi Marie², Antonio Marcondes Lenario³, Sueli Mieko Oba-Shinjo², Samuel Katsuyuki Shinjo¹

Affiliations

¹ From the Laboratory of Inflammatory Myopathies, Division of Rheumatology.
² Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo, São Paulo, Brazil.
³ Division of Metabolism, Department of Internal Medicine, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI.

PMID: 34227790
DOI: 10.1097/RHU.0000000000001721

Abstract

Background/objective: The aim of this study was to evaluate the effects of exercise training on the ubiquitin-proteasome system (UPS) and genes related to autophagy on the skeletal muscle of patients with dermatomyositis (DM) and immune-mediated necrotizing myopathies (IMNMs).

Methods: Seven DM patients and 6 IMNM patients were treated for 12 weeks with a twice-weekly aerobic and resistance training exercise program. Aerobic capacity, muscle strength, and expression of genes in the skeletal muscle related to UPS and to autophagy were evaluated at the baseline and after the intervention. Moreover, only at the baseline, 10 healthy control individuals were also evaluated.

Results: The age of DM and IMNM patients was 49.8 and 58.5 years, respectively. Genes related to UPS were upregulated, whereas genes related to autophagy and antioxidative systems were downregulated only in the DM group when compared with control group. After completion of the exercise training program, several genes related to UPS were downregulated, whereas genes related to autophagy, mitochondrial pathways, and antioxidative systems were upregulated in both the DM and IMNM groups.

Conclusions: Exercise training can increase genes related to autophagy, mitophagy, and lysosomal biogenesis in the skeletal muscle of patients. These results suggest an increase in the recycling of damaged proteins and organelles, which may also contribute to the performance and endurance of skeletal muscles in these patients. Furthermore, in patients with myositis, exercise training led to a decrease in genes related to UPS and an increase in genes related to antioxidative capacity. Therefore, this may also contribute to an attenuation of skeletal muscle loss and of the deleterious effects of oxidative stress on the skeletal muscle of these patients.

Trial registration: ClinicalTrials.gov NCT03092167.

MeSH terms

Autophagy
Exercise
Humans
Middle Aged
Muscle, Skeletal
Myositis*
Proteasome Endopeptidase Complex* / genetics
Ubiquitins

Substances

Ubiquitins
Proteasome Endopeptidase Complex

Associated data

ClinicalTrials.gov/NCT03092167