Docosahexaenoic acid counteracts palmitate-induced endoplasmic reticulum stress in C2C12 myotubes: Impact on muscle atrophy
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.
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.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/8150
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". .
. (),
December 2017.
September 21, 2023.
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," , no.
(December 2017),
http://hdl.handle.net/10342/8150 (accessed
September 21, 2023).
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. .
December 2017;
():
.
http://hdl.handle.net/10342/8150. Accessed
September 21, 2023.
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