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The Role of Class IIa HDACs in the Expression of E3 Ligases ATROGIN-1/MAFbx and MuRF1 under Muscle Unloading

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The role of histone deacetylases 4/5 (HDAC4/5) in the activation of myogenin and E3 ligases (MuRF1 and MAFbx) under functional unloading of m. soleus was studied. For this purpose, trichostatin A, a histone deacetylase inhibitor, was used in suspended rats. Wistar rats (24 three-month-old males) were divided into three groups (eight in each). One group served as a control (C), the second (HS) and third groups were suspended for 3 days (the rats of group 3 were intraperitoneally administered trichostatin A at a dose of 0.6 mg/kg of body mass per day (HST)). The rats were killed with an overdose of nembutal (75 mg/kg of mass), and m. soleus was immediately frozen in liquid nitrogen. In the HST group, a significant decrease in the HDAC4 protein content in the nuclear fraction (in contrast to the HS group) and its increase in the cytoplasmic fraction (relative to the control (p < 0.05)) were found. The administration of trichostatin A prevented changes in the HDAC4 content in the nucleus (relative to the C group), whereas the HDAC5 content was significantly reduced (p < 0.05) in the HS group. Thus, the drug prevented the effect of functional unloading on the nuclear localization of HDAC 4/5. The level of myogenin transcription factor in the HST group of rats did not differ from that in the control, while it was significantly higher in the HS group (p < 0.05). The expression of mRNA of E3 ligase atrogin-1/MAFbx in the HST rats was the same as in the control group and was significantly higher in the HS group (p < 0.05). The expression of mRNA of E3 ligase MuRF1in both groups was increased compared to the controls (regardless of the drug administration). Conclusion: HDAC4/5 regulates the expression of myogenin and E3 ligase atrogin-1/MAFbx. Inhibition of HDAC4/5 does not affect the regulation of the expression of E3 ligase MuRF1.

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ACKNOWLEDGMENTS

The work was supported by the Russian Science Foundation, project no. 18-15-00062.

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Authors and Affiliations

  1. Institute of Biomedical Problems, Russian Academy of Sciences, 123007, Moscow, Russia

    S. P. Belova, E. P. Mochalova & T. L. Nemirovskaya

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  1. S. P. Belova
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  2. E. P. Mochalova
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  3. T. L. Nemirovskaya
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Correspondence to S. P. Belova.

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All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals. The protocol of experiments was approved by the Bioethics Committee of the Institute of Biomedical Problems, Russian Academy of Sciences.

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Translated by E. Puchkov

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Belova, S.P., Mochalova, E.P. & Nemirovskaya, T.L. The Role of Class IIa HDACs in the Expression of E3 Ligases ATROGIN-1/MAFbx and MuRF1 under Muscle Unloading. Biochem. Moscow Suppl. Ser. A 14, 74–80 (2020). https://doi.org/10.1134/S1990747820010031

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  • DOI: https://doi.org/10.1134/S1990747820010031

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