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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Leucine Supplementation Decreases HDAC4 Expression and Nuclear Localization in Skeletal Muscle Fiber of Rats Submitted to Hindlimb Immobilization

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Autor(es):
Alves, Paula K. N. [1] ; Cruz, Andre [1] ; Silva, William J. [1] ; Labeit, Siegfried [2, 3] ; Moriscot, Anselmo S. [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil
[2] Univ Med Mannheim, Fac Clin Med Mannheim, Inst Integrat Pathophysiol, Univ Heidelberg, D-68169 Mannheim - Germany
[3] Myomedix GmbH, D-69151 Neckargemund - Germany
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: CELLS; v. 9, n. 12 DEC 2020.
Citações Web of Science: 0
Resumo

In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (similar to 280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (similar to 50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine. (AU)

Processo FAPESP: 15/04090-0 - Identificação e caracterização de mecanismos envolvidos no controle de massa e regeneração do músculo estriado esquelético
Beneficiário:Anselmo Sigari Moriscot
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 18/24419-4 - Efeito da leucina sobre a expressão de miR-299A e HDAC4 no músculo esquelético de ratos submetidos à imobilização: implicações para o controle de massa muscular
Beneficiário:Paula Ketilly Nascimento Alves
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 17/09398-8 - Interações entre as vias da miostatina e mTORC1 no músculo esquelético: implicações para a ação biológica do hormônio tireoidiano
Beneficiário:André Cruz de Oliveira
Linha de fomento: Bolsas no Brasil - Doutorado Direto