Palmitate-induced cell death and mitochondrial respiratory dysfunction in myoblasts are not prevented by mitochondria-targeted antioxidants

Abstract

Background/Aims: Deleterious effects of saturated fatty acids in skeletal muscle cells are well known but their impact on mitochondrial respiration has not been well studied. Mitochondrial oxidative damage has been implicated to play a role in their effect. The purpose of this study was to evaluate viability, mtDNA integrity and mitochondrial respiration in C2C12 myoblasts and myotubes exposed to palmitate and to test the effect of mitochondria-targeted antioxidants MitoQ and MitoTEMPOL in preventing palmitate-induced damage. Methods: Cells were treated with tested compounds, mtDNA damage was detected by quantitative PCR and mitochondrial respiration was measured using an extracellular flux analyzer XF24. Results: Palmitate caused mtDNA damage, which was associated with reduced mitochondrial respiration and cell death in myoblasts but not in myotubes. MitoTEMPOL was able to prevent palmitate-induced mtDNA damage in myoblasts but failed to prevent cell death. MitoQ did not show any protective effect and both compounds markedly inhibited mitochondrial respiration. Conclusion: Our results indicate that skeletal muscle progenitor cells could be the first target of the deleterious action of palmitate, as myoblasts appeared to be more sensitive to its effects than myotubes possibly in part due to a lower spare respiratory capacity in the former. Only MitoTEMPOL prevented palmitate-induced mtDNA damage but neither antioxidant was able to prevent cell death and both antioxidants had a marked negative effect on respiration. © 2014 S. Karger AG, Basel.