Comparing Atrophy‐Inducing Signals on ER Stress in C 1 C 1 2 Muscle Cells

Muscle wasting (atrophy) is a consequence of chronic diseases, such as kidney disease or diabetes, and reduces the patient's overall quality of life and functional independence. Previous studies in this lab show that muscle cells treated with palmitate (Palm, a saturated fatty acid) activates ER stress and contributes to the atrophy process. The purpose of our experiments is to determine whether ER stress is a common feature of atrophy signaling by comparing the effects of two known inducers of muscle atrophy, glucocorticoids and Palm, on ER stress markers. Glucocorticoids are elevated during physiological stress like chronic diseases and are permissive for muscle wasting. Therefore, we tested the hypothesis that glucocorticoids increase markers of ER stress. C 1 C 1 2 muscle cells were treated with 1μM Dexamethasone (DEX, a glucocorticoid) and/or 500μM of Palm. The mRNA levels of the ER stress markers ATF4 and CHOP were measured by qPCR methods. ATF4 represents one of three arms of the ER stress response and CHOP represents an integrated response of all three arms. Treating myotubes with DEX had little effect on ATF4 or CHOP mRNA levels compared to the control. Palm did not change ATF4 mRNA but, similar to previous work, Palm increased CHOP mRNA. Co‐treatment of Palm and Dex synergistically increased both ATF4 and CHOP. These results suggest that in the presence of other atrophy signals, glucocorticoids act synergistically to enhance ER stress signaling. Future studies will evaluate whether activation of ER stress in co‐treated cells prolongs cell survival. Support or Funding Information R25DK101390, VA‐MERIT I01BX001456, NIH R01 DK 95610, NIH T32 DK 007656