Down-regulation of peroxisome proliferator activated receptor γ coactivator 1α induces oxidative stress and toxicity of 1-(4-Chlorophenyl)-benzo-2,5-quinone in HaCaT human keratinocytes

- 4-ClBQ inhibits PGC-1α and catalase expression in HaCaT cells.
- pgc-1α overexpression abrogates 4-ClBQ induced reduction in catalase expression.
- pgc-1α overexpression suppresses 4-ClBQ induced oxidative stress and toxicity.

Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator that is known to regulate oxidative stress response by enhancing the expression of antioxidant genes. We have shown previously that 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a quinone-metabolite of 4-monochlorobiphenyl (PCB3) induces oxidative stress and toxicity in human skin keratinocytes, and breast and prostate epithelial cells. In this study, we investigate whether PGC-1α regulates oxidative stress and toxicity in 4-ClBQ treated HaCaT human keratinocytes. Results showed significant down-regulation in the expression of PGC-1α and catalase in 4-ClBQ treated HaCaT cells. Down-regulation of PGC-1α expression was associated with 4-ClBQ induced increase in the steady-state levels of cellular reactive oxygen species (ROS) and toxicity. Overexpression of pgc-1α enhanced the expression of catalase and suppressed 4-ClBQ induced increase in cellular ROS levels and toxicity. These results suggest that pgc-1α mediates 4-ClBQ induced oxidative stress and toxicity in HaCaT cells presumably by regulating catalase expression.

1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a metabolite of environmental pollutant 4-monochlorobiphenyl (PCB3), suppresses peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) expression, which correlates with decreases in catalase expression and activity and increases in cellular reactive oxygen species levels and toxicity in HaCaT human keratinocytes. These effects were significantly abrogated in cells overexpressing of pgc-1α.