Introduction: Severe burn induces hepatic damage and dysfunction and is associated with alterations of protein synthesis. eEF2k/eEF2 plays a key role in regulating elongation step of protein synthesis. The aim of the present study was to determine the molecular signalling mechanism that lead to an altered hepatic protein synthesis post-burn.

Methods: Sprague-Dawley rats received a full thickness burn of 60% of their total body surface area. Liver tissue was processed for Western blotting to determine eEF2k/eEF2 alterationn after burn injury in vivo. To mimic calcium alteration and subsequent ER stress after burn injury, Human hepatocellular liver carcinoma cell (HepG2) was treated with sarcoendoplasmic reticulum calcium ATPase (SERCA) inhibitor thapsigargin (TG). Cells were labeled with L-ring-13C6-Phenelylyne stable isotope and protein fractional synthetic rate (FSR) was measured by GC-MS. Protein signals were detected by SDS-PAGE and western blots, and intracellular calcium homeostasis was evaluated by calcium imaging in vitro.

Results: Burn injury caused an elevation of eEF2 kinase (eEF2K) activity by decreased its phosphorylation, leading to eukaryotic translation elongation factor 2 (eEF2) deactivated. The expression of hepatic derived albumin decreased 24hr postburn. Severe burn elevated cytosolic calcium concentrations by ER calcium depletion and caused subsequent ER stress. In vitro Hepg2 model, we found that calcium elevated in cytosol from ER and ER stress signals including p-IRE-1, Bip and p-JNK activated with 24 TG treatment, phosphor-eEF2k significantly decreased and phosphor-eEF2 correspond increased with TG treatment, protein FSR significantly decreased indicating the inhibition of hepatic protein synthesis.

Conclusion: Severe burn injury interrupts hepatic protein synthesis is associated with eEF2k/ eEF2 signal pathway.