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Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases
Author(s) -
Baptista Igor L.,
Leal Marcelo L.,
Artioli Guilherme G.,
Aoki Marcelo S.,
Fiamoncini Jarlei,
Turri Antonio O.,
Curi Rui,
Miyabara Elen H.,
Moriscot Anselmo S.
Publication year - 2010
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21578
Subject(s) - leucine , ubiquitin ligase , protein degradation , muscle atrophy , skeletal muscle , ubiquitin , soleus muscle , endocrinology , medicine , biochemistry , dna ligase , downregulation and upregulation , biology , chemistry , enzyme , amino acid , gene
The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin–proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross‐sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F‐box (MAFbx)/atrogin‐1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS‐driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization. Muscle Nerve, 2010