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

Mochalova, Ekaterina P.; Belova, Svetlana P.; Kostrominova, Tatiana Y.; Шенкман, Борис; Nemirovskaya, T. L.

doi:10.3390/ijms21134815

Cited by 15 publications

(15 citation statements)

References 41 publications

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“…Meanwhile, HDAC4/GADD45α axis also plays an important role in the prevention of muscle atrophy induced by hind limb unloading in elderly rats (Yoshihara et al, 2019 ). Recent studies have shown that HDAC4 and HDAC5 are involved in muscle atrophy induced by hind limb unloading through the regulation of myogenin (MYOG), ubiquitin, and calpain-1 (Mochalova et al, 2020 ). In conclusion, the role of HDAC4 in skeletal muscle cells is complex, and there are many regulatory molecular targets.…”

Section: Introductionmentioning

confidence: 99%

HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

Cai²,

Shen

et al. 2021

Front. Cell. Neurosci.

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Denervation can activate the catabolic pathway in skeletal muscle and lead to progressive skeletal muscle atrophy. At present, there is no effective treatment for muscle atrophy. Histone deacetylase 4 (HDAC4) has recently been found to be closely related to muscle atrophy, but the underlying mechanism of HDAC4 in denervation-induced muscle atrophy have not been described clearly yet. In this study, we found that the expression of HDAC4 increased significantly in denervated skeletal muscle. HDAC4 inhibition can effectively diminish denervation-induced muscle atrophy, reduce the expression of muscle specific E3 ubiquitin ligase (MuRF1 and MAFbx) and autophagy related proteins (Atg7, LC3B, PINK1 and BNIP3), inhibit the transformation of type I fibers to type II fibers, and enhance the expression of SIRT1 and PGC-1 α. Transcriptome sequencing and bioinformatics analysis was performed and suggested that HDAC4 may be involved in denervation-induced muscle atrophy by regulating the response to denervation involved in the regulation of muscle adaptation, cell division, cell cycle, apoptotic process, skeletal muscle atrophy, and cell differentiation. STRING analysis showed that HDAC4 may be involved in the process of muscle atrophy by directly regulating myogenin (MYOG), cell cycle inhibitor p21 (CDKN1A) and salt induced kinase 1 (SIK1). MYOG was significantly increased in denervated skeletal muscle, and MYOG inhibition could significantly alleviate denervation-induced muscle atrophy, accompanied by the decreased MuRF1 and MAFbx. MYOG overexpression could reduce the protective effect of HDAC4 inhibition on denervation-induced muscle atrophy, as evidenced by the decreased muscle mass and cross-sectional area of muscle fibers, and the increased mitophagy. Taken together, HDAC4 inhibition can alleviate denervation-induced muscle atrophy by reducing MYOG expression, and HDAC4 is also directly related to CDKN1A and SIK1 in skeletal muscle, which suggests that HDAC4 inhibitors may be a potential drug for the treatment of neurogenic muscle atrophy. These results not only enrich the molecular regulation mechanism of denervation-induced muscle atrophy, but also provide the experimental basis for HDAC4-MYOG axis as a new target for the prevention and treatment of muscular atrophy.

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Section: Introductionmentioning

confidence: 99%

HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

Cai²,

Shen

et al. 2021

Front. Cell. Neurosci.

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“…Despite the improved muscle status with the oil treatment, the increase in atrogenes, MuRF1, and atrogin-1 were not prevented by the oil mixture. It has recently been reported that HDAC-5 inhibition is able to prevent disuse-induced upregulation of atrogin-1 and myogenin, whereas HDAC-4 inhibition was only able to prevent increased myogenin expression [ 55 ]. In addition, it has been proposed that HDAC-4 deacetylates MHC proteins, allowing MuRF-1 to ubiquitinate them, triggering their proteolysis [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of a Mixture of Algae and Extra Virgin Olive Oils on the Age-Induced Alterations of Rodent Skeletal Muscle: Role of HDAC-4

et al. 2020

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Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle; it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.

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“…In this study, the N2 Bristol (wild-type) strain and RB756 hda-4 (ok518) deletion mutant were used. To synchronize the growth of the worms, an egg preparation was made in a laboratory at the Kennedy Space Center as described previously 28 . All L1 larvae (each strain, 9,000 worms) were kept in a 1-ml plastic syringe in M9 buffer containing 5 mg/L cholesterol (M9C) until the initiation of the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 1000 adult worms were collected by thawing the frozen culture samples on ice and washing them three times by natural sedimentation in ice-cold M9 buffer to remove larvae and bacterial food. RNA extraction, microarray analysis, and real-time RT-PCR analysis were performed as described previously 28 , 29 . The following primer pairs were used for PCR amplification: T28A11.19 (forward: 5ʹ-CGA GTG AGT TAG AGA GAA GAA GAA TTA GAA-3ʹ, reverse: 5ʹ-TCT GCT CCA AAT CCA GAA AAA GT-3ʹ), T28A11.2 (forward: 5ʹ-AAA AGA CAA CTG CAT GAA AAA GGA-3ʹ, reverse: 5ʹ-GCC GAC TCC GAT GAA ATG A-3ʹ), C17B7.4 (forward: 5ʹ-CGA ATT GTG CAA AAA CAT GGT T-3ʹ, reverse: 5ʹ-GCG AGT CCT CCT CTC CAC AAG-3ʹ), T20D4.11 (forward: 5ʹ-AGA ACT TGT GGA GGA GCC ATGT-3ʹ, reverse: 5ʹ-AGT CAGC GTC GCA TTG TTT G-3ʹ), T20D4.10 (forward: 5ʹ-CAG TTG CGA CTG GAG CAG AA-3ʹ, reverse: 5ʹ-GGA CAG ACC CAT GAT GCA AGA-3ʹ), C03G6.5 (forward: 5ʹ-GCATGAAGAAGGAGATTACTGAAACA-3ʹ, reverse: 5ʹ-ACC GGA AAG ATT GAC AAA TTG C-3ʹ), and eft-2 (forward: 5ʹ-GAC GCT ATC CAC AGA GGA GG-3ʹ, reverse: 5ʹ-TTC CTG TGA CCT GAG ACT CC-3ʹ).…”

Section: Methodsmentioning

confidence: 99%

“…The level of the H3K27me3 modification is controlled by cooperation with histone deacetylases (HDACs) and methyltransferases (HMT) 25 , 26 . In particular, class IIa HDACs 4 and 5 in rat skeletal muscles are activated by hindlimb suspension, and it leads to decreased expression of myosin heavy chain and increased expression of MuRF-1 and MAFbox E3-ligases, which are involved in rat muscular atrophy 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

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Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans

et al. 2021

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Epigenetic changes during long-term spaceflight are beginning to be studied by NASA’s twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase (hda)-4 mutants. Expression levels of 39 genes were consistently upregulated in all four generations of adult hda-4 mutants grown under microgravity compared with artificial Earth-like gravity (1G). In contrast, in the wild type, microgravity-induced upregulation of these genes occurred a little. Among these genes, 11 contain the domain of unknown function 19 (DUF-19) and are located in a cluster on chromosome V. When compared with the 1G condition, histone H3 trimethylation at lysine 27 (H3K27me3) increased under microgravity in the DUF-19 containing genes T20D4.12 to 4.10 locus in wild-type adults. On the other hand, this increase was also observed in the hda-4 mutant, but the level was significantly reduced. The body length of wild-type adults decreased slightly but significantly when grown under microgravity. This decrease was even more pronounced with the hda-4 mutant. In ground-based experiments, one of the T20D4.11 overexpressing strains significantly reduced body length and also caused larval growth retardation and arrest. These results indicate that under microgravity, C. elegans activates histone deacetylase HDA-4 to suppress overregulation of several genes, including the DUF-19 family. In other words, the expression of certain genes, including negative regulators of growth and development, is epigenetically fine-tuned to adapt to the space microgravity.

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

Cited by 15 publications

References 41 publications

HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

Beneficial Effects of a Mixture of Algae and Extra Virgin Olive Oils on the Age-Induced Alterations of Rodent Skeletal Muscle: Role of HDAC-4

Histone deacetylase HDA-4-mediated epigenetic regulation in space-flown C. elegans

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