title: 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.
abstract: 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.
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Wusheng
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: prabhat-goswami@uiowa.edu.
authors.forename: Prabhat C
authors.initials: PC
authors.lastname: Goswami
mesh_terms: D016227:Benzoquinones / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000597136:1-(4-chlorophenyl)-benzo-2,5-quinone; D016227:Benzoquinones; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D002374:Catalase
keywords: Catalase; Oxidative stress; PCB3; PCB3-quinone; PGC-1α; Polychlorinated biphenyls