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Article

Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading

by
Ekaterina P. Mochalova
1,
Svetlana P. Belova
1,
Tatiana Y. Kostrominova
2,
Boris S. Shenkman
1 and
Tatiana L. Nemirovskaya
1,*
1
Institute of Biomedical Problems, RAS, 123007 Moscow, Russia
2
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine-Northwest, Gary, IN 46408, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4815; https://doi.org/10.3390/ijms21134815
Submission received: 28 May 2020 / Revised: 3 July 2020 / Accepted: 4 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Modifications of Molecular Structure and Interactions in Epigenome)
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Abstract

Unloading leads to skeletal muscle atrophy via the upregulation of MuRF-1 and MAFbx E3-ligases expression. Reportedly, histone deacetylases (HDACs) 4 and 5 may regulate the expression of MuRF1 and MAFbx. To examine the HDAC-dependent mechanisms involved in the control of E3-ubiquitin ligases expression at the early stages of muscle unloading we used HDACs 4 and 5 inhibitor LMK-235 and HDAC 4 inhibitor Tasqinimod (Tq). Male Wistar rats were divided into four groups (eight rats per group): nontreated control (C), three days of unloading/hindlimb suspension (HS) and three days HS with HDACs inhibitor LMK-235 (HSLMK) or Tq (HSTq). Treatment with LMK-235 diminished unloading-induced of MAFbx, myogenin (MYOG), ubiquitin and calpain-1 mRNA expression (p < 0.05). Tq administration had no effect on the expression of E3-ligases. The mRNA expression of MuRF1 and MAFbx was significantly increased in both HS and HSTq groups (1.5 and 4.0 folds, respectively; p < 0.05) when compared with the C group. It is concluded that during three days of muscle unloading: (1) the HDACs 4 and 5 participate in the regulation of MAFbx expression as well as the expression of MYOG, ubiquitin and calpain-1; (2) the inhibition of HDAC 4 has no effect on MAFbx expression. Therefore, HDAC 5 is perhaps more important for the regulation of MAFbx expression than HDAC 4.
Keywords: muscle unloading; HDACs 4 and 5; MYOG; MuRF1; MAFbx muscle unloading; HDACs 4 and 5; MYOG; MuRF1; MAFbx

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MDPI and ACS Style

Mochalova, E.P.; Belova, S.P.; Kostrominova, T.Y.; Shenkman, B.S.; Nemirovskaya, T.L. Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading. Int. J. Mol. Sci. 2020, 21, 4815. https://doi.org/10.3390/ijms21134815

AMA Style

Mochalova EP, Belova SP, Kostrominova TY, Shenkman BS, Nemirovskaya TL. Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading. International Journal of Molecular Sciences. 2020; 21(13):4815. https://doi.org/10.3390/ijms21134815

Chicago/Turabian Style

Mochalova, Ekaterina P., Svetlana P. Belova, Tatiana Y. Kostrominova, Boris S. Shenkman, and Tatiana L. Nemirovskaya. 2020. "Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading" International Journal of Molecular Sciences 21, no. 13: 4815. https://doi.org/10.3390/ijms21134815

APA Style

Mochalova, E. P., Belova, S. P., Kostrominova, T. Y., Shenkman, B. S., & Nemirovskaya, T. L. (2020). Differences in the Role of HDACs 4 and 5 in the Modulation of Processes Regulating MAFbx and MuRF1 Expression during Muscle Unloading. International Journal of Molecular Sciences, 21(13), 4815. https://doi.org/10.3390/ijms21134815

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