Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation.
Acta Physiol (Oxf)
; 222(4): e13003, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29178319
ABSTRACT
AIM:
Based 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.METHODS:
To 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.RESULTS:
After 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 (~35%, P < .001 vs Control), enhancing the effect of T3 (from ~12% 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.CONCLUSION:
Our results indicate that MDM2 might be involved in the pro-trophic effects of T3 in skeletal muscle.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triyodotironina
/
Fibras Musculares de Contracción Lenta
/
Proteínas Proto-Oncogénicas c-mdm2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Acta Physiol (Oxf)
Asunto de la revista:
FISIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Brasil