CoCl 2 -simulated hypoxia in skeletal muscle cell lines: Role of free radicals in gene up-regulation and induction of apoptosis

Since it was suggested that cobalt chloride (CoCl2) could mimic the O2 sensing role of mitochondria by increasing reactive oxygen species (ROS) generation during normoxia, we studied the correlation between CoCl2-generation of free radicals and the induction of a hypoxic cellular response in myogenic cell lines. In both L6C5 and C2C12 cell lines, exposure to CoCl2 induced an increase of intracellular oxidants, the accumulation of HIF-1α protein, and the expression of vascular endothelial growth factor (VEGF) and/or iNOS genes. On the other hand, only ascorbic acid, but not trolox, was effective in lowering the CoCl2 gene up-regulation. Neither the cytotoxicity nor the apoptosis induced by CoCl2 in skeletal muscle cells were modified by culture supplementation with either ascorbic acid or trolox. Thus, CoCl2 treatment of myogenic cell lines may represent a useful and convenient in vitro model to study gene modulation induced by hypoxia in skeletal muscle, although cellular loss induced by this metal may in...