Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Dong Suk Yoon; Yoorim Choi; Dong Seok Cha; Peng Zhang; Seong Mi Choi; Mohammad Abdulmohsen Alfhili; Joseph Ryan Polli; De Qwon Pendergrass; Faten A. Taki; Brahmam Kapalavavi; Xiaoping Pan; Baohong Zhang; T. Keith Blackwell; Jin Woo Lee; Myon Hee Lee

doi:10.1038/s41598-017-12719-3

Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Dong Suk Yoon, Yoorim Choi, Dong Seok Cha, Peng Zhang, Seong Mi Choi, Mohammad Abdulmohsen Alfhili, Joseph Ryan Polli, De Qwon Pendergrass, Faten A. Taki, Brahmam Kapalavavi, Xiaoping Pan, Baohong Zhang, T. Keith Blackwell, Jin Woo Lee, Myon Hee Lee

Department of Orthopaedic Surgery

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

26 Citations (Scopus)

Abstract

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment.

Original language	English
Article number	12592
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12719-3
Publication status	Published - 2017 Dec 1

Bibliographical note

Funding Information:
We thank the members of the Lee laboratory, Jiwoo Lee and Jiah Lee (St. Peter Catholic School, Greenville, NC), and Dr. Lim (ECU), for helpful advice and discussion during this work. This work was supported in part by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI14C2000) to J.W.L., NIH grants GM062891 and AG54215 to TKB, a Diabetes Research Center award (P30DK036836) to the Joslin Diabetes Center, as well as the Brody Brother’s Grant (BBE 213152), Brody Seed/Bridge Grant, and NIH (1R15GM112174-01A1) to M-H.L. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440).

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© 2017 The Author(s).

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Yoon, D. S., Choi, Y., Cha, D. S., Zhang, P., Choi, S. M., Alfhili, M. A., Polli, J. R., Pendergrass, D. Q., Taki, F. A., Kapalavavi, B., Pan, X., Zhang, B., Blackwell, T. K., Lee, J. W., & Lee, M. H. (2017). Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells. Scientific reports, 7(1), Article 12592. https://doi.org/10.1038/s41598-017-12719-3

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title = "Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells",

abstract = "Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment.",

author = "Yoon, {Dong Suk} and Yoorim Choi and Cha, {Dong Seok} and Peng Zhang and Choi, {Seong Mi} and Alfhili, {Mohammad Abdulmohsen} and Polli, {Joseph Ryan} and Pendergrass, {De Qwon} and Taki, {Faten A.} and Brahmam Kapalavavi and Xiaoping Pan and Baohong Zhang and Blackwell, {T. Keith} and Lee, {Jin Woo} and Lee, {Myon Hee}",

note = "Funding Information: We thank the members of the Lee laboratory, Jiwoo Lee and Jiah Lee (St. Peter Catholic School, Greenville, NC), and Dr. Lim (ECU), for helpful advice and discussion during this work. This work was supported in part by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI14C2000) to J.W.L., NIH grants GM062891 and AG54215 to TKB, a Diabetes Research Center award (P30DK036836) to the Joslin Diabetes Center, as well as the Brody Brother{\textquoteright}s Grant (BBE 213152), Brody Seed/Bridge Grant, and NIH (1R15GM112174-01A1) to M-H.L. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

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Yoon, DS, Choi, Y, Cha, DS, Zhang, P, Choi, SM, Alfhili, MA, Polli, JR, Pendergrass, DQ, Taki, FA, Kapalavavi, B, Pan, X, Zhang, B, Blackwell, TK, Lee, JW & Lee, MH 2017, 'Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells', Scientific reports, vol. 7, no. 1, 12592. https://doi.org/10.1038/s41598-017-12719-3

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AU - Yoon, Dong Suk

AU - Choi, Yoorim

AU - Cha, Dong Seok

AU - Zhang, Peng

AU - Choi, Seong Mi

AU - Alfhili, Mohammad Abdulmohsen

AU - Polli, Joseph Ryan

AU - Pendergrass, De Qwon

AU - Taki, Faten A.

AU - Kapalavavi, Brahmam

AU - Pan, Xiaoping

AU - Zhang, Baohong

AU - Blackwell, T. Keith

AU - Lee, Jin Woo

AU - Lee, Myon Hee

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PY - 2017/12/1

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N2 - Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment.

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Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Abstract

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