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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The effect of HDAC inhibitor, 4b, on skeletal muscle gene expression

ABSTRACT: To assess the effects of histone deacetylase (HDAC) inhibitor, HDACi 4b, treatment on muscle function on a molecular level, we performed microarray analysis on skeletal muscle (gastrocnemius) samples from wt and N17182Q mice treated with the HDAC inhibitor 4b for 3 months (50 mg/kg; s.c. injection 3x weekly; n=4 per group). The transcriptome pattern in N17182Q mice compared to wt controls consisted of deficits in the expression of genes related to mitochondrial function and oxidative metabolism. In addition, we noted that numerous genes associated with basal contractile function were altered in HD N17182Q mice. These include genes related to the muscle contractile complex, Tnnt3 and Myh8, as well as several additional myosin genes: myosin heavy chain genes, Myh10 and Myh4, and myosin light chain genes, Myl1, Mylc2 and Mylk. These findings implicate deficits in the underlying contractile function in skeletal muscle from HD mice. Further, we found robust effects of 4b treatment on the expression of genes in skeletal muscle, with 556 genes showing significantly altered expression, at p<0.005, in 4b-treated N17182Q muscle compared to vehicle-treated control mice. n=4 vehicle-treated WT mice, n=5 HDACi 4b-treated WT mice, n=4 vehicle-treated N17182Q transgenic mice, and n=3 HDACi 4b-treated N17182Q transgenic mice.

ORGANISM(S): Mus musculus

SUBMITTER: Giovanni Coppola

PROVIDER: E-GEOD-56963 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The effect of HDAC inhibitor, 4b, on skeletal muscle gene expression

Project description:To assess the effects of histone deacetylase (HDAC) inhibitor, HDACi 4b, treatment on muscle function on a molecular level, we performed microarray analysis on skeletal muscle (gastrocnemius) samples from wt and N17182Q mice treated with the HDAC inhibitor 4b for 3 months (50 mg/kg; s.c. injection 3x weekly; n=4 per group). The transcriptome pattern in N17182Q mice compared to wt controls consisted of deficits in the expression of genes related to mitochondrial function and oxidative metabolism. In addition, we noted that numerous genes associated with basal contractile function were altered in HD N17182Q mice. These include genes related to the muscle contractile complex, Tnnt3 and Myh8, as well as several additional myosin genes: myosin heavy chain genes, Myh10 and Myh4, and myosin light chain genes, Myl1, Mylc2 and Mylk. These findings implicate deficits in the underlying contractile function in skeletal muscle from HD mice. Further, we found robust effects of 4b treatment on the expression of genes in skeletal muscle, with 556 genes showing significantly altered expression, at p<0.005, in 4b-treated N17182Q muscle compared to vehicle-treated control mice.

2014-11-01 | GSE56963 | GEO

p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival

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The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice

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Blocking muscle wasting via deletion of the muscle specific E3 ligase MuRF1 impedes pancreatic tumor growth – ubiquitome dataset

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The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice

2010-12-27 | GSE26317 | GEO

KH_dKO: Simultaneous loss of skeletal muscle myosin heavy chain IIx and IIb causes severe hypoplasia of skeletal muscles in young mice

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2022-09-28 | PXD035107 | Pride

Fast skeletal myosin binding protein-C regulates fast skeletal muscle contraction

Project description:Fast skeletal myosin binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and is predominantly expressed in fast skeletal muscle. Mutations in the gene that encodes fMyBP-C, MYBPC2, is associated with distal arthrogryposis, while fMyBP-C protein is reduced in diseased muscle. However, the functional and structural roles of fMyBP-C in skeletal muscle remain unclear. To address this gap, we generated a homozygous fMyBP-C knockout mouse (C2-/-) and characterized it, both in vivo and in vitro. Ablation of fMyBP-C was benign in terms of muscle weight, fiber type, cross-sectional area, and sarcomere ultrastructure. However, grip strength and plantar-flexor muscle strength were significantly decreased in C2-/- compared to WT. Peak isometric tetanic force (Po) and isotonic speed of contraction were significantly reduced in isolated extensor digitorum longus (EDL) from C2-/- mice. In EDL muscles of C2-/- mice, small-angle X-ray diffraction revealed significant increase in equatorial intensity ratio (I1.1/I1.0) during contraction, indicating a greater degree of myosin head shift towards actin while MLL4 layer-line intensity was decreased at rest, indicating less ordered myosin heads at rest. Interfilament lattice spacing was also significantly increased in C2-/- EDL muscle compared to WT. Consistent with these findings, we observed a significant reduction of steady-state isometric force during Ca2+ activations, myofilament calcium sensitivity, sinusoidal stiffness in skinned EDL muscle fibers from C2-/- mice. Finally, C2-/- muscles displayed disruption of inflammatory and regenerative genes and increased muscle damage upon mechanical overload. Together, our data suggest that fMyBP-C is essential for maximal speed and force of contraction, sarcomere integrity, and calcium sensitivity in fast twitch muscle.

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