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Title: Selenoprotein P regulates 1-(4-Chlorophenyl)-benzo-2,5-quinone-induced oxidative stress and toxicity in human keratinocytes.

Authors: Xiao, Wusheng; Zhu, Yueming; Sarsour, Ehab H; Kalen, Amanda L; Aykin-Burns, Nukhet; Spitz, Douglas R; Goswami, Prabhat C

Published In Free Radic Biol Med, (2013 Dec)

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.

PubMed ID: 23770201 Exiting the NIEHS site

MeSH Terms: Benzoquinones/toxicity*; Cell Line; Environmental Pollutants/toxicity*; Flow Cytometry; Humans; Immunoblotting; Keratinocytes/drug effects; Keratinocytes/metabolism*; Oligonucleotide Array Sequence Analysis; Oxidative Stress/physiology*; Real-Time Polymerase Chain Reaction; Selenoprotein P/metabolism*

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