title: Selenoprotein P regulates 1-(4-Chlorophenyl)-benzo-2,5-quinone-induced oxidative stress and toxicity in human keratinocytes.
abstract: Polychlorinated biphenyls and their metabolites are environmental pollutants that are believed to have adverse health effects presumably by inducing oxidative stress. To determine if 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ; metabolite of 4-monochlorobiphenyl, PCB3)-induced oxidative stress is associated with changes in the expression of specific antioxidant genes, mRNA levels of 92 oxidative stress-response genes were analyzed using TaqMan Array Human Antioxidant Mechanisms (Life Technologies), and results were verified by performing quantitative RT-PCR assays. The expression of selenoprotein P (sepp1) was significantly downregulated (8- to 10-fold) in 4-ClBQ-treated HaCaT human skin keratinocytes, which correlated with a significant increase in MitoSOX oxidation. Overexpression of Mn-superoxide dismutase or catalase or treatment with N-acetyl-l-cysteine suppressed 4-ClBQ-induced toxicity. Sodium selenite supplementation also suppressed 4-ClBQ-induced decrease in sepp1 expression, which was associated with a significant inhibition in cell death. Furthermore, HaCaT cells overexpressing sepp1 were resistant to 4-ClBQ-induced oxidative stress and toxicity. These results demonstrate that SEPP1 represents a previously unrecognized regulator of PCB-induced biological effects. These results support the speculation that selenoproteins can be an attractive countermeasure for PCB-induced adverse biological effects.
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; Department of Radiation Oncology, Feinberg Northwestern Medical School, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Ehab H
authors.initials: EH
authors.lastname: Sarsour
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Kalen
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA; Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Nukhet
authors.initials: N
authors.lastname: Aykin-Burns
authors.affiliation: Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
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*; D002460:Cell Line; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D051149:Selenoprotein P / Q000378:metabolism*
chemical_list: C000597136:1-(4-chlorophenyl)-benzo-2,5-quinone; D016227:Benzoquinones; D004785:Environmental Pollutants; D051149:Selenoprotein P
keywords: 1-(4-Chlorophenyl)-benzo-2,5-quinone; 4-ClBQ; 4-monochlorobiphenyl; AdCAT; AdEmpty; AdMnSOD; Free radicals; HaCaT; MFI; N-acetyl-L-cysteine; NAC; Oxidative stress; PCB3; PEG-CAT; PEG-SOD; Polychlorinated biphenyls; ROS; SECIS; SEPP1; Selenoprotein P; adenovirus carrying a control vector without an insert; adenovirus carrying a human Mn-superoxide dismutase cDNA; adenovirus carrying a human catalase cDNA; mean fluorescence intensity; polyethylene glycol–catalase; polyethylene glycol–superoxide dismutase; reactive oxygen species; selenocysteine insertion sequence; selenoprotein P