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Trichostatin A inhibits skeletal muscle atrophy induced by cigarette smoke exposure in mice. 2019

Jingjing Ding, and Fang Li, and Yanfei Cong, and Jianing Miao, and Di Wu, and Bo Liu, and Lili Wang
Medical Research Center of Shengjing Hospital, China Medical University, Shenyang 110004, China; Key Laboratory of Research and Application of Animal Model for Environmental and Metabolic Diseases, Liaoning Province, China.

OBJECTIVE It is well known that cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD) accompanied by skeletal muscle atrophy. Histone deacetylases (HDACs) that remove acetyl groups from target proteins are necessary for the muscle atrophy associated with skeletal muscle disuse. However, the role of HDACs and trichostatin A (TSA), a HDAC inhibitor, in skeletal muscle atrophy caused by CS exposure remains poorly understood. METHODS Female mice were exposed to CS twice daily for 40 days and TSA injected intraperitoneally into CS-exposed mice on alternate days. Skeletal muscles were weighed and gastrocnemius (Gas) muscle histomorphology examined by hematoxylin and eosin staining. Histone deacetylases 1 and 2 (HDAC1/2), and markers of ubiquitin degradation, muscle differentiation, apoptosis, pyroptosis, and the cytoskeletal proteins were assessed by western blot and immunohistochemistry in Gas. RESULTS CS exposure decreased body and skeletal muscle weights and triggered an increase in the percentage of fiber with centralized nuclei in Gas. HDAC1/2 proteins were upregulated in the Gas of mice exposed to CS, while TSA effectively inhibited HDAC1/2 protein levels and attenuated the loss of body weight and skeletal muscle wet weight induced by CS exposure. Markers for ubiquitin degradation, muscle differentiation, cytoskeletal proteins, apoptosis and pyroptosis were all upregulated following CS exposure and effectively restored by TSA. CONCLUSIONS TSA may inhibit skeletal muscle atrophy and histomorphological alterations induced by CS exposure by downregulating markers of ubiquitin degradation, muscle fiber differentiation, cytoskeletal proteins, apoptosis and pyroptosis via HDAC1/2 inhibition.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009133 Muscular Atrophy Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. Atrophy, Muscle,Neurogenic Muscular Atrophy,Neurotrophic Muscular Atrophy,Atrophies, Muscle,Atrophies, Muscular,Atrophies, Neurogenic Muscular,Atrophies, Neurotrophic Muscular,Atrophy, Muscular,Atrophy, Neurogenic Muscular,Atrophy, Neurotrophic Muscular,Muscle Atrophies,Muscle Atrophy,Muscular Atrophies,Muscular Atrophies, Neurogenic,Muscular Atrophies, Neurotrophic,Muscular Atrophy, Neurogenic,Muscular Atrophy, Neurotrophic,Neurogenic Muscular Atrophies,Neurotrophic Muscular Atrophies
D003598 Cytoskeletal Proteins Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. Proteins, Cytoskeletal
D005260 Female Females
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012907 Smoking Willful or deliberate act of inhaling and exhaling SMOKE from burning substances or agents held by hand. Smoking Behaviors,Smoking Habit,Behavior, Smoking,Behaviors, Smoking,Habit, Smoking,Habits, Smoking,Smoking Behavior,Smoking Habits
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056284 Histone Deacetylase 1 A histone deacetylase subtype that is found along with HISTONE DEACETYLASE 2; RETINOBLASTOMA-BINDING PROTEIN 4; and RETINOBLASTOMA-BINDING PROTEIN 7 as core components of histone deacetylase complexes. HDAC1 Histone Deacetylase,RPD3L1 Histone Deacetylase,Deacetylase 1, Histone,Deacetylase, HDAC1 Histone,Deacetylase, RPD3L1 Histone,Histone Deacetylase, HDAC1,Histone Deacetylase, RPD3L1

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