| Full text | |
| Author(s): |
Cruz, Andre
[1]
;
Ferian, Andrea
[1]
;
Alves, Paula K. N.
[1]
;
Silva, William Jose
[1]
;
Bento, Mirella Ribeiro
[1]
;
Gasch, Alexander
[2]
;
Labeit, Siegfried
[2]
;
Moriscot, Anselmo Sigari
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil
[2] Heidelberg Univ, Inst Integrat Pathophysiol, Fac Clin Med Mannheim, Mannheim - Germany
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | DNA AND CELL BIOLOGY; v. 39, n. 12 NOV 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by real-time PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling. (AU) | |
| FAPESP's process: | 12/22488-2 - Expression of microRNAs in the skeletal muscle plasticity: the possible interrelationships with MuRFs effect in the regenerative process |
| Grantee: | William Jose da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 13/19387-2 - Regulation of GSK3-beta/Beta-catenin in skeletal muscle of rats supplemented with leucine and subjected to atrophy |
| Grantee: | Mirella Ribeiro Bento |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 15/04090-0 - Identification and caracterization of mechanisms involved in skeletal muscle mass control and regeneration |
| Grantee: | Anselmo Sigari Moriscot |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/09398-8 - Interplay betweeen myostatin and mTORC1 pathways in skeletal muscle: implications for a thyroid hormone biological action |
| Grantee: | André Cruz de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 18/24419-4 - Effect of leucine on the expression of miR-299A and HDAC4 in the skeletal muscle of rats submitted to immobilization: implications for the control of muscle mass |
| Grantee: | Paula Ketilly Nascimento Alves |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |