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-1 alpha (HIF-1 alpha), 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-1 alpha activator, dimethyloxalylglycine (DMOG), respectively. Changes in HIF-1 alpha, MAPK/ERK signaling pathway, and postmor-tem metabolism levels were measured in muscles collected from all time points. Oxidative stress significantly activated MAPK/ERK pathway and increased HIF-1 alpha 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-1 alpha accumulation and glycolysis. Interestingly, this attenuation could be bypassed by DMOG (P < 0.05). Altogether, MAPK/ERK-dependent maintenance and enhancement of HIF-1 alpha nuclear accu-mulation promotes postmortem metabolism during early postmortem under oxidative stress. These findings provide valuable information on postmortem metabolism that HIF-1 alpha regulates glycolysis under oxidative stress and suggest that HIF-1 alpha can serve as a target for controlling postmortem glycolysis.

Automated summary

This study found that nuclear accumulation of HIF-1α through the MAPK/ERK pathway promotes early postmortem metabolism under oxidative stress and regulates glycolysis. These findings contribute to a better understanding of postmortem metabolism and suggest HIF-1α as a potential target for controlling postmortem glycolysis.