Disuse-induced nuclear accumulation of histone deacetylase 4 in rat skeletal muscle

2018 ◽  
Vol 3 ◽  
Keyword(s):  
Skeletal Muscle ◽  
Histone Deacetylase ◽  
Nuclear Accumulation ◽  
Rat Skeletal Muscle ◽  
Histone Deacetylase 4

scholarly journals Dephosphorylation and Caspase Processing Generate Distinct Nuclear Pools of Histone Deacetylase 4

2007 ◽  
Vol 27 (19) ◽  
pp. 6718-6732 ◽  
Author(s):  
Gabriela Paroni ◽  
Alessandra Fontanini ◽  
Nadia Cernotta ◽  
Carmela Foti ◽  
Mahesh P. Gupta ◽  
...  
Keyword(s):  
Cell Death ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Proteolytic Processing ◽  
Chromatin Interaction ◽  
Nuclear Accumulation ◽  
Stable Complex ◽  
Extracellular Signals ◽  
Repressive Effect ◽  
Histone Deacetylase 4

ABSTRACT From the nucleus, histone deacetylase 4 (HDAC4) regulates a variety of cellular processes, including growth, differentiation, and survival, by orchestrating transcriptional changes. Extracellular signals control its repressive influence mostly through regulating its nuclear-cytoplasmic shuttling. In particular, specific posttranslational modifications such as phosphorylation and caspase-mediated proteolytic processing operate on HDAC4 to promote its nuclear accumulation or export. To understand the signaling properties of this deacetylase, we investigated its cell death-promoting activity and the transcriptional repression potential of different mutants that accumulate in the nucleus. Here we show that, compared to that of other nuclear forms of HDAC4, a caspase-generated nuclear fragment exhibits a stronger cell death-promoting activity coupled with increased repressive effect on Runx2- or SRF-dependent transcription. However, this mutant displays reduced repressive action on MEF2C-driven transcription. Photobleaching experiments and quantitative analysis of the raw data, based on a two-binding-state compartmental model, demonstrate the existence of two nuclear pools of HDAC4 with different chromatin-binding properties. The caspase-generated fragment is weakly bound to chromatin, whereas an HDAC4 mutant defective in 14-3-3 binding or the wild-type HDAC5 protein forms a more stable complex. The tightly bound species show an impaired ability to induce cell death and repress Runx2- or SRF-dependent transcription less efficiently. We propose that, through specific posttranslation modifications, extracellular signals control two distinct nuclear pools of HDAC4 to differentially dictate cell death and differentiation. These two nuclear pools of HDAC4 are characterized by different repression potentials and divergent dynamics of chromatin interaction.

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

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2582
Author(s):  
Paula K. N. Alves ◽  
André Cruz ◽  
William J. Silva ◽  
Siegfried Labeit ◽  
Anselmo S. Moriscot
Keyword(s):  
Skeletal Muscle ◽  
Target Genes ◽  
Marked Decrease ◽  
Mrna Levels ◽  
Rna Seq ◽  
Rat Skeletal Muscle ◽  
Leucine Supplementation ◽  
Male Wistar Rats ◽  
Histone Deacetylase 4 ◽  
The Impact

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 (~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 (~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.

scholarly journals Histone deacetylase 4 protects from denervation and skeletal muscle atrophy in a murine model of amyotrophic lateral sclerosis

EBioMedicine ◽  
2019 ◽  
Vol 40 ◽  
pp. 717-732 ◽  
Author(s):  
Eva Pigna ◽  
Elena Simonazzi ◽  
Krizia Sanna ◽  
Krzysztof Marian Bernadzki ◽  
Tomek Proszynski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amyotrophic Lateral Sclerosis ◽  
Histone Deacetylase ◽  
Muscle Atrophy ◽  
Murine Model ◽  
Skeletal Muscle Atrophy ◽  
Histone Deacetylase 4 ◽  
Lateral Sclerosis

scholarly journals Immobilization induces nuclear accumulation of HDAC4 in rat skeletal muscle

2016 ◽  
Vol 66 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Toshinori Yoshihara ◽  
Shuichi Machida ◽  
Yuka Kurosaka ◽  
Ryo Kakigi ◽  
Takao Sugiura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nuclear Accumulation ◽  
Rat Skeletal Muscle

Nuclear accumulation of histone deacetylase 4 (HDAC4) by PP1-mediated dephosphorylation exerts neurotoxicity in Pb-exposed neural cells

2020 ◽  
Vol 81 ◽  
pp. 395-405
Author(s):  
Xiaozhen Gu ◽  
Xiyao Huang ◽  
Danyang Li ◽  
Nanxi Bi ◽  
Xi Yu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Nuclear Accumulation ◽  
Neural Cells ◽  
Histone Deacetylase 4
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