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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation

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Author(s):
Ramos, G. V. [1] ; Cruz, A. [1] ; Silva, W. J. [1] ; Rozanski, A. [1] ; Baptista, I. L. [1] ; Silvestre, J. G. [1] ; Moriscot, A. S. [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: ACTA PHYSIOLOGICA; v. 222, n. 4 APR 2018.
Web of Science Citations: 1
Abstract

AimBased upon a microarray assay, we have identified that triiodothyronine (T3) upregulates MDM2 gene expression in the rat skeletal muscle. As MDM2 protein is an E3 ligase, we hypothesized that this enzyme could play a role in T3 effects on skeletal muscle mass control. MethodsTo test our hypothesis, male rats (2 months old) were randomly assigned into the following groups: intact controls, treated with 20 physiological doses of T3 for 0.5, 1 and 7 days, or with 5, 20 and 50 physiological doses of T3 for 7 days. For in vitro experiments, myotubes and C2C12 cells were treated with T3 for 3 days. ResultsAfter validation of the microarray finding throughout RT-PCR and confirmation that T3 induces increases in MDM2 protein expression in a dose-dependent manner, we observed that MDM2 was upregulated by T3 exclusively in fibre type I. Moreover, detailed histological evaluation showed that MDM2 overexpression distributes punctiformily along the cross section of the fibre and also inside nuclei. MDM2 colocalizes with PAX7 in control muscle and T3 downregulates this myogenic factor. Pharmacological inhibition of MDM2 in cultured myotubes caused a severe decrease in their diameter (similar to 35%, P < .001 vs Control), enhancing the effect of T3 (from similar to 12% to similar to 35%, P < .001) alone upon myotube diameter and mRNA levels of atrogenes. Finally, we observed that FOXO3 (MDM2 target) is kept outside the nucleus under T3 stimulation. ConclusionOur results indicate that MDM2 might be involved in the pro-trophic effects of T3 in skeletal muscle. (AU)

FAPESP's process: 12/13071-0 - Cellular bases of the anti-atrophic effects of leucine in the skeletal muscle: role of VPS34
Grantee:Igor Luchini Baptista
Support Opportunities: Scholarships in Brazil - Post-Doctoral
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: 12/13315-7 - Role of MuRF1 and MuRF2 in skeletal muscle myogenic cell differentiation
Grantee:João Guilherme de Oliveira Silvestre
Support Opportunities: Scholarships in Brazil - Doctorate
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: 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