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    Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy

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    Author
    Woodworth-Hobbs, Myra E.; Perry, Ben D.; Rahnert, Jill A.; Hudson, Matthew B.; Zheng, Bin; Price, S. Russ
    Abstract
    Lipid accumulation in skeletal muscle results in dysregulation of protein meta- bolism and muscle atrophy. We previously reported that treating C2C12 myo- tubes with palmitate (PA), a saturated fatty acid, increases the overall rate of proteolysis via activation of the ubiquitin-proteasome and autophagy systems; co-treatment with the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents the PA-induced responses. Others have reported that PA induces endoplasmic reticulum (ER) stress which initiates the unfolded pro- tein response (UPR), a collective group of responses that can lead to activa- tion of caspase-mediated proteolysis and autophagy. Presently, we tested the hypothesis that DHA protects against PA-induced ER stress/UPR and its atro- phy-related responses in muscle cells. C2C12 myotubes were treated with 500 lmol/L PA and/or 100 lmol/L DHA for 24 h. Proteins and mRNA asso- ciated with ER stress/UPR, autophagy, and caspase-3 activation were evalu- ated. PA robustly increased the phosphorylation of protein kinase R (PKR)- like ER kinase (PERK) and eukaryotic initiation factor 2a (eIF2a). It also increased the mRNAs encoding activating transcription factor 4 (ATF4), spliced X-box binding protein 1 (XBP1s), C/EBP homologous protein (CHOP), and autophagy-related 5 (Atg5) as well as the protein levels of the PERK target nuclear factor erythroid 2-related factor (Nrf2), CHOP, and cleaved (i.e., activated) caspase-3. Co-treatment with DHA prevented all of the PA-induced responses. Our results indicate that DHA prevents PA- induced muscle cell atrophy, in part, by preventing ER stress/UPR, a process that leads to activation of caspase-mediated proteolysis and an increase in expression of autophagy-related genes.
    URI
    http://hdl.handle.net/10342/8150
    Date
    2017-12
    Citation:
    APA:
    Woodworth-Hobbs, Myra E., & Perry, Ben D., & Rahnert, Jill A., & Hudson, Matthew B., & Zheng, Bin, & Price, S. Russ. (December 2017). Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy. Physiological Reports, (5:23), p.. Retrieved from http://hdl.handle.net/10342/8150

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    MLA:
    Woodworth-Hobbs, Myra E., and Perry, Ben D., and Rahnert, Jill A., and Hudson, Matthew B., and Zheng, Bin, and Price, S. Russ. "Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy". Physiological Reports. 5:23. (.), December 2017. August 16, 2022. http://hdl.handle.net/10342/8150.
    Chicago:
    Woodworth-Hobbs, Myra E. and Perry, Ben D. and Rahnert, Jill A. and Hudson, Matthew B. and Zheng, Bin and Price, S. Russ, "Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy," Physiological Reports 5, no. 23 (December 2017), http://hdl.handle.net/10342/8150 (accessed August 16, 2022).
    AMA:
    Woodworth-Hobbs, Myra E., Perry, Ben D., Rahnert, Jill A., Hudson, Matthew B., Zheng, Bin, Price, S. Russ. Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy. Physiological Reports. December 2017; 5(23) . http://hdl.handle.net/10342/8150. Accessed August 16, 2022.
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