Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistr...

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Autores principales:	Yoon TH, Kim MJ, Suh YJ, Lim EJ, Kim RK, Woo SJ, Hyun KH, Kwon DW, Yoon CH, Yoo KC, Lee SJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0f43d82a2b0d4d77b865522f34c99018
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spelling	oai:doaj.org-article:0f43d82a2b0d4d77b865522f34c990182021-12-02T06:30:31ZTitanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation1176-91141178-2013https://doaj.org/article/0f43d82a2b0d4d77b865522f34c990182012-03-01T00:00:00Zhttp://www.dovepress.com/titanium-dioxide-induces-apoptotic-cell-death-through-reactive-oxygen--a9403https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25&ndash;70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25&ndash;70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.Keywords: TiO2, reactive oxygen species, apoptotic cell death, Fas upregulation, Bax activation, mitochondrial membrane potential loss, caspase activationYoon THKim MJSuh YJLim EJKim RKWoo SJHyun KHKwon DWYoon CHYoo KCLee SJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1203-1214 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yoon TH Kim MJ Suh YJ Lim EJ Kim RK Woo SJ Hyun KH Kwon DW Yoon CH Yoo KC Lee SJ Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
description	Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25&ndash;70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25&ndash;70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.Keywords: TiO2, reactive oxygen species, apoptotic cell death, Fas upregulation, Bax activation, mitochondrial membrane potential loss, caspase activation
format	article
author	Yoon TH Kim MJ Suh YJ Lim EJ Kim RK Woo SJ Hyun KH Kwon DW Yoon CH Yoo KC Lee SJ
author_facet	Yoon TH Kim MJ Suh YJ Lim EJ Kim RK Woo SJ Hyun KH Kwon DW Yoon CH Yoo KC Lee SJ
author_sort	Yoon TH
title	Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
title_short	Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
title_full	Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
title_fullStr	Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
title_full_unstemmed	Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation
title_sort	titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated fas upregulation and bax activation
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/0f43d82a2b0d4d77b865522f34c99018
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Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

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