Hypoxia-inducible factor-1α nuclear accumulation via a MAPK/ERK-dependent manner partially explains the accelerated glycogen metabolism in yak longissimus dorsi postmortem under oxidative stress

Although exhaustive studies have established that oxidative stress is a key contributor to accelerated postmortem metabolism, the specific reasons remain fully undefined. We hypothesized that nuclear accumulation of hypoxia-inducible factor-1α (HIF-1α), a significant transcription factor for energy metabolism, regulates postmortem glycolysis under oxidative stress. Postmortem yak longissimus dorsi (LD) muscles were incubated with saline, hydrogen peroxide (H2O2), H2O2 plus MAPK/ERK inhibitor (U0126), or H2O2 plus U0126 and HIF-1α activator, dimethyloxalylglycine (DMOG), respectively. Changes in HIF-1α, MAPK/ERK signaling pathway, and postmortem metabolism levels were measured in muscles collected from all time points. Oxidative stress significantly activated MAPK/ERK pathway and increased HIF-1α expression and nuclear translocation (P < 0.05) although its mRNA levels were hardly affected (P > 0.05). Additionally, oxidative stress enhanced early postmortem muscle metabolism (P < 0.05). These effects were substantially weakened by U0126 treatment, which prevented oxidative stress-induced HIF-1α accumulation and glycolysis. Interestingly, this attenuation could be bypassed by DMOG (P < 0.05). Altogether, MAPK/ERK-dependent maintenance and enhancement of HIF-1α nuclear accumulation promotes postmortem metabolism during early postmortem under oxidative stress. These findings provide valuable information on postmortem metabolism that HIF-1α regulates glycolysis under oxidative stress and suggest that HIF-1α can serve as a target for controlling postmortem glycolysis.