Imoxin, a PKR inhibitor, ameliorates ER stress induced by palmitate or tunicamycin in C2C12 myotubes

Abstract

Prevalence of obesity has increased worldwide for decades and has becomes a major public health issue. Obesity is a key inducer of endoplasmic reticulum stress (ER stress), insulin resistance and sarcopenia. ER stress cause accumulation of unfolded or misfolded proteins leading to an unfolded protein response (UPR). Chronically prolonged ER stress consequently can interfere with insulin signaling and cell survival. The double‐stranded RNA (dsRNA)‐activated protein kinase R (PKR) plays a significant role in mediating inflammation, insulin sensitivity and glucose homeostasis. However, pathological roles of PKR in ER stress in muscle cells under obese condition is not fully understood. The current study aimed to investigate the effect of imoxin, a PKR inhibitor, on ER stress induced by palmitate or tunicamycin in C2C12 myotubes. The cells were treated with imoxin at 5 uM with or without bovine serum albumin (BSA)‐conjugated palmitate at 0.5mM or 500 ng/ml tunicamycin for 24 hr. Levels of ER stress signaling proteins including CHOP and BiP were measured by Western blotting. Palmitate significantly augmented the protein levels of both CHOP (288 ± 56%) and BiP (224 ± 17%) compared with BSA control. However, imoxin treatment attenuated palmitate‐induced ER stress signaling (140 ± 30% for CHOP and 89 ± 4% for BiP compared with control, respectively). Similarly, tunicamycin treated cells showed higher protein levels of CHOP (1132 ± 96%) and BiP (794 ± 34%) than control. Imoxin treatment prevented tunicamycin‐induced ER stress signaling (67 ± 40% for CHOP and 245 ± 27% for BiP compared with control, respectively). Thus, these results suggest that palmitate and tunicamycin induce ER stress through PKR in muscle cells.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.