Hochuekkito accelerates recovery from cisplatin induced-muscle atrophy accompanied by slow-twitch fiber-specific microRNA upregulation in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE295648 | GEO | 2025/05/15
REPOSITORIES: GEO
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Project description:Hochuekkito accelerates recovery from cisplatin induced-muscle atrophy accompanied by slow-twitch fiber-specific microRNA upregulation in mice
| PRJNA1255521 | ENA
Project description:Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue lacking effective treatment. Hindlimb unloading is a commonly used model for muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particular from the perspective of myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with MS2 name) differentially expressed between HU group and CON group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, and pathways like histidine, taurine, and hypotaurine metabolism were linked to muscle atrophy. Protein and metabolism joint analysis revealed that some pathways such as glutathione metabolism, ferroptosis and lysosome pathways were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analysis. The upregulation of proteins which are expressed in fast-twitch fibers indicated the conversion of slow-twitch fibers to fast-twitch fibers under HU. Some metabolism-related proteins have been screened out. Besides, some differentially abundant metabolites and pathways revealed the important role of metabolism in the muscle atrophy of soleus. Our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating the proteomics and metabolomics of soleus muscles.
2025-05-07 | PXD057671 | Pride
Project description:Loss of muscle mass and function—a hallmark of skeletal muscle aging—is known as sarcopenia. Moreover, mammalian aging is reportedly driven by loss of epigenetic information. However, the effect of epigenetic alterations on skeletal muscle homeostasis is unknown. In this study, we show that chronic elevation of global DNA methylation results in a myopathy-like phenotype and age-related changes in skeletal muscle. Overexpression of muscle de novo methyltransferase 3a (Dnmt3a) increased central nucleus-positive myofibers, predominantly in fast-twitch myofibers, and shifted muscle fiber type to stress-resistant slow-twitch myofibers, accompanied by increased inflammatory and senescent signatures, decreased mitochondrial OXPHOS complex I protein level, and reduced basal autophagy in skeletal muscle. Chronic Dnmt3a overexpression decreased muscle mass and strength, and impaired tolerance to endurance exercise with age. This age-related decline in endurance exercise capacity was accompanied by an augmented inflammatory signature in a manner that is enhanced with age and promoted muscle atrophy. Network analysis identified Akt1 as a potential hub gene. Dnmt3a expression not only reduced sensitivity to starvation-induced muscle atrophy by suppressing the FoxO-regulated autophagy and ubiquitin–proteasome systems, but also reduced the restorability from starvation-induced muscle atrophy. These data suggest that increased global DNA methylation disrupts skeletal muscle homeostasis, promotes age-related muscle atrophy, and reduces muscle metabolic elasticity.
2025-01-16 | GSE262342 | GEO
Project description:Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to simultaneously contract multiple muscle groups. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly via mitochondrial biosynthesis. In this study, we examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for 1 week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague Dawley rats using belt electrodes attached to both ankle joints. In acute stimulation, a significant decrease in glycogen content in the left and right TA and GAS was observed, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES also enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN+electrically stimulated with B-SES (DEN＋ES) groups. After 7 days of treatment, muscle wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN+ES groups compared to those in the CON group. The DEN+ES group showed significantly higher muscle weight and CSA than the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial and ribosome biogenesis are key events in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 45S (n = 6) levels in the DEN+ES group were higher than those in the DEN group. The mRNA levels of the muscle proteolytic molecules Atrogin-1 and MuRF1 were significantly higher in DEN than in CONT but were suppressed in DEN+ES. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes was effective in preventing denervation-induced atrophy in multiple muscle groups. Unlike twitch contractions, ribosomal biosynthesis plays a key role in tetanic contractions to prevent muscle atrophy.
2024-01-06 | E-MTAB-13286 | biostudies-arrayexpress
Project description: In fish, the slow-twitch skeletal muscle fibres have an oxidative metabolism, present peripherical location in the red muscle, and are used for sustained movements. They may respond to alterations in food availability differently than the fast-twitch muscle. The aim of this manuscript was to study the slow-twitch muscle fibres of Piaractus Mesopotamicus, a neotropical fish, submitted to 30 days of fasting (D30) followed by one day (D31) or 30 days of refeeding (D60). The treated animals were compared with regularly fed fish. To verify the presence of atrophy and hypertrophy, we performed histological analysis of muscle fibre diameter in D30 and D60, and RT-qPCR gene expression analysis of catabolic (murfa, murfb, mafbx) and anabolic genes (igf-1, mTOR) in D30, D31 and D60. The gene expression of the allergen and Ca2+-carrier parvalbumin (pvalb) was also measured in D30, D31 and D60. The proteome of slow-twitch fibres at D30 and D60 was obtained by shotgun proteomics (digestion of proteins with trypsin followed by LC-MS/MS identification), and the proteins differentially expressed were used to construct protein interaction networks. The histological analysis showed no difference between treated fish in relation to the control. The expression of catabolic and anabolic genes was not changed, except for the negative regulation of igf-1 in D30 and of mtor in D31. The expression of pvalb was not changed in D30 and D60, but it was decreased in D31. The proteomic analysis identified 169 proteins in D30 (24 upregulated and 18 downregulated) and 170 proteins in D60 (17 upregulated and 21 downregulated). Many of them were related to energetic metabolism, including lipid metabolism, as shown by the protein network analysis. These results enlarge our understanding of the acclimation of slow-twitch fibres to changes in nutrient availability and set a path for future research.
2019-11-28 | PXD014320 | Pride
Project description:Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. Fast-twitch and slow-twitch muscles are differentially affected in ALS patients and in the SOD1-G93A model, fast-twitch muscles being more vulnerable. We used miRNA microarrays to investigate miRNA alterations in fast-twitch (EDL) and slow-twitch (soleus) skeletal muscles of symptomatic SOD1-G93A animals and their age-matched wild type littermates.
2014-03-04 | GSE55507 | GEO
Project description:Skeletal muscle is highly developed after birth, consisting of glycolytic fast- and oxidative slow-twitch fibers; however, the mechanisms of fiber type-specific differentiation are poorly understood. Here, we found an unexpected role for mitochondrial fission in the differentiation of fast-twitch oxidative fibers. Depletion of the mitochondrial fission factor dynamin-related protein 1 (Drp1) in mouse skeletal muscle and cultured myotubes resulted in the specific reduction of fast-twitch muscle fibers independently of respiratory function. Altered mitochondrial fission caused the activation of the Akt/mammalian target of rapamycin (mTOR) pathway via the mitochondrial accumulation of mTOR complex 2 (mTORC2), and rapamycin administration rescued the reduction of fast-twitch fibers in vivo and in vitro. Under Akt/mTOR activation, the mitochondria-related cytokine growth differentiation factor-15 was upregulated, which repressed fast-twitch fiber differentiation. Our findings reveal a novel role for mitochondrial dynamics in the activation of mTORC2 on mitochondria, resulting in the differentiation of muscle fibers.
2023-04-01 | GSE228362 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. Fast-twitch and slow-twitch muscles are differentially affected in ALS patients and in the SOD1-G93A model, fast-twitch muscles being more vulnerable. We used miRNA microarrays to investigate miRNA alterations in fast-twitch (EDL) and slow-twitch (soleus) skeletal muscles of symptomatic SOD1-G93A animals and their age-matched wild type littermates. At age of 90 days RNA was extracted from extensor digitorum longus (EDL) and soleus (SOL) muscles of male SOD1-G93A animals and their age-matched wild type male littermates. RNA was hybridized on Affymetrix Multispecies miRNA-2_0 Array.
2014-03-04 | E-GEOD-55507 | biostudies-arrayexpress
Project description:The right legs of 3 months old CD1 mice were denervated by unilaterally cutting the sciatic nerve at the level of trochanter, resulting in a permanent denervation of the lower hindleg. At the indicated times, animals were killed by cervical dislocation and tibialis anterior (TA) muscles were dissected out and frozen in liquid nitrogen. The expression analysis was carried out at five time points, namely just after denervation (time 0) and 1, 3, 7 and 14 days after nerve interruption. The contralateral, left TA muscle from the same individual served as innervated control. We reversed labeling of denervated and contralateral samples in each experiment, thus carrying out two separate hybridizations for each time point. Keywords = mouse Keywords = fast-twitch muscle Keywords = denervation Keywords = atrophy Keywords: time-course
2005-09-21 | GSE1893 | GEO
Project description:Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle fiber proteins that associate with Gadd45a as it induces skeletal muscle atrophy in living mice. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, the MAP kinase kinase kinase MEKK4. Furthermore, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into way that skeletal muscle atrophy occurs at the molecular level.
2016-05-17 | MSV000079730 | MassIVE