HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy

Beharry, Adam W.; Sandesara, Pooja B.; Roberts, Brandon M.; Ferreira, Leonardo F.; Senf, Sarah M.; Judge, Sarah M.

doi:10.1242/jcs.136390

Cited by 102 publications

(128 citation statements)

References 67 publications

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“…Additionally, reduced HDAC3 is associated with mitochondrial biogenesis, and HDAC3‐specific deletion in skeletal muscle or class I‐specific inhibitors could be used to understand the role of mitochondrial biogenesis in age‐related muscle atrophy and metabolic disease. And lastly, inhibition of HDAC1 prevents muscle atrophy from disuse (Beharry et al ., 2014). If sarcopenia results from lack of exercise and movement during aging, inhibition of HDAC1 will prevent muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Mice deficient in HDAC4 and HDAC5 are protected against muscle loss in a surgical model of denervation; these mice do not upregulate the muscle‐specific E3 ligases MuRF1 or atrogin‐1 in response to denervation (Moresi et al ., 2010). Furthermore, HDAC1, a class I HDAC, induces muscle atrophy in response to disuse and nutrient deprivation (Beharry et al ., 2014). Thus, histone deacetylases are an attractive target for diseases that result in muscle atrophy.…”

Section: Introductionmentioning

confidence: 99%

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The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Walsh¹,

et al. 2015

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SummarySarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with loss of motor neuron innervation, we investigated the potential for the histone deacetylase (HDAC) inhibitor butyrate to modulate age‐related muscle loss. Consistent with previous studies, we found significant loss of hindlimb muscle mass in 26‐month‐old C57Bl/6 female mice fed a control diet. Butyrate treatment starting at 16 months of age wholly or partially protected against muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross‐sectional area and prevented intramuscular fat accumulation in the old mice. In addition to the protective effect on muscle mass, butyrate reduced fat mass and improved glucose metabolism in 26‐month‐old mice as determined by a glucose tolerance test. Furthermore, butyrate increased markers of mitochondrial biogenesis in skeletal muscle and whole‐body oxygen consumption without affecting activity. The increase in mass in butyrate‐treated mice was not due to reduced ubiquitin‐mediated proteasomal degradation. However, butyrate reduced markers of oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data is the first to show a beneficial effect of butyrate on muscle mass during aging and suggests HDACs contribute to age‐related muscle atrophy and may be effective targets for intervention in sarcopenia and age‐related metabolic disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Walsh¹,

et al. 2015

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“…FOXO proteins are deacetylated by HDACs and sirtuins simultaneously. Certain studies indicate that class I and II HDACs regulate FOXO nuclear localization and transcriptional activation in response to nutrient deprivation (79). However, compared with class II, class I HDACs preferentially regulate the activity of FOXO proteins.…”

Section: Acetylation Of Foxo Proteinsmentioning

confidence: 99%

“…It has been reported that HDAC1 is a primary regulator of FOXO in skeletal muscle and a key regulator of the atrophy. Furthermore, HDAC1-mediated deacetylation of FOXO in the cytosol may be a major signal that leads to decreased phosphorylation and nuclear localization of FOXO (79). Research has demonstrated that reducing FOXO3a acetylation may lead to FOXO3a-dependent transcriptional activation and induce atrophy of muscle fibers (81,82).…”

Section: Acetylation Of Foxo Proteinsmentioning

confidence: 99%

Post-translational modifications of FOXO family proteins

Wang

Huang

2016

Molecular Medicine Reports

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Abstract. The Forkhead box O (FOXO) protein family is predominantly involved in apoptosis, oxidative stress, DNA damage/repair, tumor angiogenesis, glycometabolism, regulating life span and other important biological processes. Its activity is affected by a variety of posttranslational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, methylation and glycosylation. When cells are subjected to different environments, the corresponding PTMs act on the FOXO protein family, to change transcriptional activity or subcellular localization, and the expression of downstream target genes, will ultimately affect the biological behavior of the cells. In this review, we will discuss the biological characteristics of FOXO protein PTMs.

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“…The hypothesis that HDACs might play a role in the mechanisms leading to neuronal toxicity after PCB exposure is substantiated by several neurologic studies. One study shows that aminomethyl]-benzamide], a class I histone deacetylase inhibitor (Beharry et al, 2014), reduces cell death following traumatic brain injury (Cao et al, 2013). Likewise, another study indicates that inhibition of class II histone deacetylases in the spinal cord attenuates inflammatory hyperalgesia (Bai et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

MS-275 Inhibits Aroclor 1254–Induced SH-SY5Y Neuronal Cell Toxicity by Preventing the Formation of the HDAC3/REST Complex on the Synapsin-1 Promoter

Formisano

Guida

Laudati

et al. 2014

J Pharmacol Exp Ther

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Polychlorinated biphenyl (PCB) exposure has been associated with neurodegenerative diseases, such as Parkinson's disease, amyotrophic lateral sclerosis, and dementia. Neuronal death elicited by the PCB mixture Aroclor 1254 (A1254) has been attributed to an increase in RE-1-silencing transcription factor (REST), which, in turn, correlates with a decrease in the synapsin-1 promoter gene. Although histone deacetylase (HDAC) inhibitors are known to be neuroprotective in several neurologic disorders, the core mechanisms governing this effect are not yet understood. Here, to examine howinhibitors prevent A1254-induced neuronal cell death, we exposed SH-SY5Y neuroblastoma cells to A1254. Exposure to A1254 (30.6 mM) for 24 and 48 hours resulted in a time-dependent cell death. Indeed, after 48 hours, MS-275, but not MC-1568, reverted A1254-induced cell death in a dose-dependent manner. Furthermore, A1254 significantly increased HDAC3, but not HDAC1 or HDAC2. Interestingly, REST physically interacted with HDAC3 after A1254 exposure. Chromatin immunoprecipitation assays revealed that MS-275 reverted the increased levels of HDAC3 binding and decreased acetylation of histone H3 within the synapsin-1 promoter region, thus reverting synapsin-1 mRNA reduction. Moreover, REST knockdown by small interfering RNA (siRNA) prevented HDAC3 from binding to the synapsin-1 promoter. Likewise, HDAC3 siRNA significantly reduced A1254-induced cell toxicity in SH-SY5Y cells and cortical neurons. Hence, this study demonstrates that inhibition of HDAC class I attenuates A1254-induced neuronal cell death by preventing HDAC3 binding and histone deacetylation within the synapsin-1 promoter region.

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HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy

Cited by 102 publications

References 67 publications

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Post-translational modifications of FOXO family proteins

MS-275 Inhibits Aroclor 1254–Induced SH-SY5Y Neuronal Cell Toxicity by Preventing the Formation of the HDAC3/REST Complex on the Synapsin-1 Promoter

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