Hypoxia-inducible factor (HIF) is thought to play an important role in regulating gene-expression in response to ischemia/reperfusion (I/R). While activation of HIF-1 is mainly attributed to hypoxia, HIF-2 has been reported to play a role in the response to hypoglycemia. Here we studied activation of HIF-1 and HIF-2 in skeletal muscle cell culture by Western Blot and RNA analysis. Our results indicate that both HIF-1 and HIF-2 were activated in myotubes by hypoglycemia, hypoxia and ischemia whereas myoblasts did not respond to hypoglycemia. Both, myoblasts and myotubes, express comparable amounts of HIF-1alpha and HIF-2alpha mRNA, but the HIF-target genes ADM, VEGF, GLUT-4, LDH and pyruvate kinase are expressed in different amounts in myoblasts and differentiated myotubes. All target genes show an induction under hypoxia but responses to hypoglycemia and ischemia vary between myotubes and myoblasts. This may contribute to the difference in survival and to regenerative processes in skeletal muscle after hypoxia or ischemia.

The study was supported by a grant from the Deutsche Forschungsgemeinschaft (Fa 225/20-2) within the SPP 1151