Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy

Author(s)

Foresto, Camila Silva ; Paula-Gomes, Silvia ; Silveira, Wilian Assis ; Graca, Flavia Aparecida ; Kettelhut, Isis do Carmo ; Pinheiro Goncalves, Dawit Albieiro ; Mattiello-Sverzut, Ana Claudia

• Document type: Journal article
• Source: Journal of Applied Physiology; v. 121, n. 3, p. 646-660, SEP 1 2016.
• Web of Science Citations: 3

Abstract

Muscle loss occurs following injury and immobilization in adulthood and childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response in infants. This work investigated first the morphological and molecular mechanisms involved in immobilization-induced atrophy in soleus muscles from rats at different stages of postnatal development {[}i.e., weanling (WR) and adult (AR) rats] and, second, the role of autophagy in regulating muscle plasticity during immobilization. Hindlimb immobilization for 10 days reduced muscle mass and fiber cross-sectional area, with more pronounced atrophy in WR, and induced slow-to-fast fiber switching. These effects were accompanied by a decrease in markers of protein synthesis and an increase in autophagy. The ubiquitin (Ub)-ligase MuRF1 and the ubiquitinated proteins were upregulated by immobilization in AR while the autolyzed form of mu-calpain was increased in WR. To further explore the role of autophagy in muscle abnormalities, AR were concomitantly immobilized and treated with colchicine, which blocks autophagosome-lysosome fusion. Colchicine-treated immobilized muscles had exacerbated atrophy and presented degenerative features. Despite Igf1/Akt signaling was downregulated in immobilized muscles from both age groups, Foxo1 and 4 phosphorylation was increased in WR. In the same group of animals, Foxo1 acetylation and Foxo1 and 4 content was increased and decreased, respectively. Our data show that muscle disorders induced by 10-day-immobilization occur in both age-dependent and -independent manners, an understanding that may optimize treatment outcomes in infants. We also provide further evidence that the strong inhibition of autophagy may be ineffective for treating muscle atrophy. (AU)

• FAPESP's process: 10/11015-0 - Intracellular mechanisms involved in anticatabolic effect of the epinephrine in skeletal muscle of fasted rats
• Grantee: Flávia Aparecida Graça
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/24524-6 - Control of muscle mass by cAMP signaling pathway
• Grantee: Isis Do Carmo Kettelhut
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 12/18861-0 - FOXO HYPERACETYLATION AS A MECHANISM OF SUPPRESSION OF ATROPHY GENE PROGRAM INDUCED BY BETA2-ADRENERGIC SIGNALING IN RODENT SKELETAL MUSCLE
• Grantee: Dawit Albieiro Pinheiro Gonçalves
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/08553-9 - The role of the beta-arrestin signaling pathway in the control of cardiac muscle mass and cardiomyocytes culture of rodents
• Grantee: Sílvia de Paula Gomes
• Support type: Scholarships in Brazil - Post-Doctorate