Skeletal muscle HIF-1α expression is dependent on muscle fiber type

Oxygen homeostasis is an essential regulation system for cell energy production and survival. The oxygen-sensitive subunit alpha of the hypoxia inducible factor-1 (HIF-1) complex is a key protein of this system. In this work, we analyzed mouse and rat HIF-1 alpha protein and mRNA expression in parallel to energetic metabolism variations within skeletal muscle. Two physiological situations were studied using HIF-1 alpha-specific Western blotting and semiquantitative RT-PCR. First, we compared HIF-1 alpha expression between the predominantly oxidative soleus muscle and three predominantly glycolytic muscles. Second, HIF-1 alpha expression was assessed in an energy metabolism switch model that was based on muscle disuse. These two in vivo situations were compared with the in vitro HIF-1 alpha induction by CoCl2 treatment on C2C12 mouse muscle cells. HIF-1 alpha mRNA and protein levels were found to be constitutively higher in the more glycolytic muscles compared with the more oxidative muscles. Our results gave rise to the hypothesis that the oxygen homeostasis regulation system depends on the fiber type.