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

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

doi:10.1016/j.freeradbiomed.2013.06.010

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

Wusheng Xiao, Yueming Zhu, Ehab H. Sarsour, Amanda L. Kalen, Nukhet Aykin-Burns, Douglas R. Spitz, Prabhat C. Goswami^*

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	70-77
Number of pages	8
Journal	Free Radical Biology and Medicine
Volume	65
DOIs	https://doi.org/10.1016/j.freeradbiomed.2013.06.010
State	Published - 2013

Funding

We thank Professors Raymond F. Burk and Kristina E. Hill at the Vanderbilt University for the 7C1 pBluescript DNA, Professors Larry W. Robertson and Hans J. Lehmler at the Occupational & Environmental Health University of Iowa for providing us with PCB3 and its metabolite 4-ClBQ, and the staff at the Flow Cytometry and the Radiation and Free Radical Research Core facilities. This study was supported by NIEHS P42ES013661 and NIH 2R01CA111365 . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government.

Keywords

4-ClBQ
Free radicals
HaCaT
Oxidative stress
PCB3
Polychlorinated biphenyls
Selenoprotein P

ASJC Scopus subject areas

Physiology (medical)
Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.freeradbiomed.2013.06.010

Cite this

@article{b4d8658f783f4b4c9771ca1c0118307b,

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.",

keywords = "4-ClBQ, Free radicals, HaCaT, Oxidative stress, PCB3, Polychlorinated biphenyls, Selenoprotein P",

author = "Wusheng Xiao and Yueming Zhu and Sarsour, {Ehab H.} and Kalen, {Amanda L.} and Nukhet Aykin-Burns and Spitz, {Douglas R.} and Goswami, {Prabhat C.}",

note = "Funding Information: We thank Professors Raymond F. Burk and Kristina E. Hill at the Vanderbilt University for the 7C1 pBluescript DNA, Professors Larry W. Robertson and Hans J. Lehmler at the Occupational & Environmental Health University of Iowa for providing us with PCB3 and its metabolite 4-ClBQ, and the staff at the Flow Cytometry and the Radiation and Free Radical Research Core facilities. This study was supported by NIEHS P42ES013661 and NIH 2R01CA111365 . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. ",

year = "2013",

doi = "10.1016/j.freeradbiomed.2013.06.010",

language = "English (US)",

volume = "65",

pages = "70--77",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Selenoprotein P regulates 1-(4-Chlorophenyl)-benzo-2,5-quinone-induced oxidative stress and toxicity in human keratinocytes

AU - Xiao, Wusheng

AU - Zhu, Yueming

AU - Sarsour, Ehab H.

AU - Kalen, Amanda L.

AU - Aykin-Burns, Nukhet

AU - Spitz, Douglas R.

AU - Goswami, Prabhat C.

N1 - Funding Information: We thank Professors Raymond F. Burk and Kristina E. Hill at the Vanderbilt University for the 7C1 pBluescript DNA, Professors Larry W. Robertson and Hans J. Lehmler at the Occupational & Environmental Health University of Iowa for providing us with PCB3 and its metabolite 4-ClBQ, and the staff at the Flow Cytometry and the Radiation and Free Radical Research Core facilities. This study was supported by NIEHS P42ES013661 and NIH 2R01CA111365 . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - 4-ClBQ

KW - Free radicals

KW - HaCaT

KW - Oxidative stress

KW - PCB3

KW - Polychlorinated biphenyls

KW - Selenoprotein P

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AN - SCOPUS:84884567653

SN - 0891-5849

VL - 65

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EP - 77

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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