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

Wusheng Xiao; Prabhat C Goswami

doi:10.1016/j.tiv.2015.05.009

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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

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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

Wusheng Xiao and Prabhat C Goswami

Toxicology in vitro, Vol.29(7), pp.1332-1338

10/2015

DOI: 10.1016/j.tiv.2015.05.009

PMCID: PMC4553100

PMID: 26004620

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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.

Catalase - metabolism

Transcription Factors - metabolism

Cell Line

Keratinocytes - drug effects

Oxidative Stress

Keratinocytes - metabolism

Down-Regulation

Humans

Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

Benzoquinones - toxicity

Transcription Factors - genetics

Details

Title: Subtitle: 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
Creators: Wusheng Xiao - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA
Prabhat C Goswami - 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
Resource Type: Journal article
Publication Details: Toxicology in vitro, Vol.29(7), pp.1332-1338
DOI: 10.1016/j.tiv.2015.05.009
PMID: 26004620
PMCID: PMC4553100
NLM abbreviation: Toxicol In Vitro
ISSN: 0887-2333
eISSN: 1879-3177
Publisher: England
Grant note: P30 ES005605 / NIEHS NIH HHS P20 CA091709 / NCI NIH HHS P42ES013661 / NIEHS NIH HHS R01 CA111365 / NCI NIH HHS 2R01CA111365 / NCI NIH HHS
Language: English
Date published: 10/2015
Academic Unit: Radiation Oncology
Record Identifier: 9984047734102771

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