1. Notch pathway activation contributes to inhibition of C2C12 myoblast differentiation by ethanol
- Author
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Elena I. Kudryavtseva, Albert K. Tai, Eric C. Wooten, Michelle A. Arya, Gordon S. Huggins, and Christopher Parkin
- Subjects
Anatomy and Physiology ,Transcription, Genetic ,Microarrays ,Cellular differentiation ,Muscle Fibers, Skeletal ,Gene Expression ,lcsh:Medicine ,MyoD ,Cell Fusion ,Myoblasts ,Mice ,0302 clinical medicine ,Basic Helix-Loop-Helix Transcription Factors ,Myocyte ,HES1 ,lcsh:Science ,Musculoskeletal System ,0303 health sciences ,Multidisciplinary ,Receptors, Notch ,Organic Compounds ,Myogenesis ,Cell Differentiation ,musculoskeletal system ,Chemistry ,Muscle ,Medicine ,Myogenin ,Public Health ,Alcohol ,C2C12 ,tissues ,Research Article ,Signal Transduction ,Notch signaling pathway ,Down-Regulation ,Biology ,Molecular Genetics ,03 medical and health sciences ,Genetics ,Animals ,Gene Networks ,Cell Shape ,MyoD Protein ,030304 developmental biology ,Homeodomain Proteins ,Ethanol ,Gene Expression Profiling ,Organic Chemistry ,lcsh:R ,Computational Biology ,Molecular biology ,High-Throughput Screening Assays ,Alcohols ,Transcription Factor HES-1 ,lcsh:Q ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myogenin expression, and microarray analysis identified ethanol activation of the Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells. Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI) abrogated induction of Hes1. On a morphological level GSI treatment completely rescued myogenic fusion defects and partially restored other myotube parameters in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast differentiation and the inhibition of myogenic fusion is mediated by Notch pathway activation.
- Published
- 2013