Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul 16;9(1):10263.
doi: 10.1038/s41598-019-46753-0.

Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading

Ekaterina P Mochalova  1 , Svetlana P Belova  1 , Timur M Mirzoev  1 , Boris S Shenkman  1 , Tatiana L Nemirovskaya  2
Affiliations

Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading

Ekaterina P Mochalova et al. Sci Rep. .

Abstract

It is known that MuRF-1 and atrogin-1/MAFbx mRNA expression is increased in rat soleus muscle under unloading conditions. We aimed to determine the role of histone deacetylase 1 (HDAC1) in the activation of MuRF-1 and MAFbx expression in rat soleus muscle at the early stage of hindlimb suspension (HS). To this end, male Wistar rats (195-215 g) were divided into 3 groups (n = 8/group): control (C), 3-day HS (HS) and 3-day HS + HDAC1 inhibitor CI-994 (1 mg/kg/day) (HS + CI). Protein content and mRNA expression levels of regulatory molecules were determined by Western-blotting and RT-PCR. CI-994 treatment prevented HS-induced increase in HDAC1 nuclear content. As expected, 3-day HS induced a significant upregulation in MAFbx, MuRF-1 and ubiquitin. CI-994 administration resulted in an attenuation of HS-mediated increase in MAFbx and ubiquitin expression levels but did not affect MuRF-1 expression. A decrease in histone acetyltransferase p300 nuclear content in the HS group was prevented by CI-994 administration. There were no significant differences in the content of phosphorylated anabolic signaling molecules between HS group and HS + CI group. Thus, inhibition of HDAC1 prevented a HS-mediated increase in MAFbx and ubiquitin expression, but did not affect MuRF-1 gene expression.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Soleus weight-to-body weight ratio. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05).
Figure 2
Figure 2
The content of calpain-1 in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05).
Figure 3
Figure 3
Representative western blots for Calpain-1, HDAC1, P300, Ac-H3, GAPDH and Lamin B in cytoplasmic and nuclear fractions.
Figure 4
Figure 4
The level of eEF2 phosphorylation in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05).
Figure 5
Figure 5
The content of phosphorylated Akt (S473) (A) and FoxO3 (S253) (B) in rat soleus muscle. С –control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05).
Figure 6
Figure 6
Nuclear content of HDAC1 in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05), #significant difference from the HS group (p < 0.05).
Figure 7
Figure 7
Cytoplasmic content of  HDAC1 in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05), #significant difference from the HS group (p < 0.05).
Figure 8
Figure 8
Nuclear content of Ac-H3 in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05), #significant difference from the HS group (p < 0.05).
Figure 9
Figure 9
Nuclear content of histone acetyltransferase p300 in rat soleus muscle. С – control, HS – 3-day hindlimb suspension + placebo, HS + CI – 3-day hindlimb suspension + CI-994 (HDAC1 inhibitor). All values are means ± SE, n = 8/group. *significant difference from control (p < 0.05), #significant difference from the HS group (p < 0.05).
See this image and copyright information in PMC

References

    1. Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am. J. Phys. End. Metab. 2014;307:469–484. - PMC - PubMed
    1. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat. Cell Biol. 2003;5:87–90. doi: 10.1038/ncb0203-87. - DOI - PubMed
    1. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int. J. Biochem. Cell Biol. 2005;37:1974–1984. doi: 10.1016/j.biocel.2005.04.018. - DOI - PubMed
    1. Jackman RW, Kandarian SC. The molecular basis of skeletal muscle atrophy. Am. J. Physiol. Cell Physiol. 2004;287:834–43. doi: 10.1152/ajpcell.00579.2003. - DOI - PubMed
    1. Cohen S, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J. Cell Biol. 2009;185:1083–95. doi: 10.1083/jcb.200901052. - DOI - PMC - PubMed

Publication types