Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies

Liping Zou, Guiping Cheng, Chengcheng Xu, Heyu Liu, Yingying Wang, Nianyu Li, Xiaorong Fan, Changhong Zhu, Wei Xia Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Wei XiaInstitute of R...

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Autores principales:	Zou L, Cheng G, Xu C, Liu H, Wang Y, Li N, Fan X, Zhu C, Xia W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	copper nanoparticles cytotoxicity oxidative stress heme oxygenase 1 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/521f1d9f5cd1434280961f2d2a66bb93
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spelling	oai:doaj.org-article:521f1d9f5cd1434280961f2d2a66bb932021-12-02T16:01:07ZCopper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies1178-2013https://doaj.org/article/521f1d9f5cd1434280961f2d2a66bb932021-02-01T00:00:00Zhttps://www.dovepress.com/copper-nanoparticles-induce-oxidative-stress-via-the-heme-oxygenase-1--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Liping Zou, Guiping Cheng, Chengcheng Xu, Heyu Liu, Yingying Wang, Nianyu Li, Xiaorong Fan, Changhong Zhu, Wei Xia Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Wei XiaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86 27 8369 2651Email tjxiawei@hust.edu.cnPurpose: The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage.Methods: Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment.Results: Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes.Conclusion: CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.Keywords: copper nanoparticles, cytotoxicity, oxidative stress, heme oxygenase 1Zou LCheng GXu CLiu HWang YLi NFan XZhu CXia WDove Medical Pressarticlecopper nanoparticlescytotoxicityoxidative stressheme oxygenase 1Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1565-1573 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	copper nanoparticles cytotoxicity oxidative stress heme oxygenase 1 Medicine (General) R5-920
spellingShingle	copper nanoparticles cytotoxicity oxidative stress heme oxygenase 1 Medicine (General) R5-920 Zou L Cheng G Xu C Liu H Wang Y Li N Fan X Zhu C Xia W Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
description	Liping Zou, Guiping Cheng, Chengcheng Xu, Heyu Liu, Yingying Wang, Nianyu Li, Xiaorong Fan, Changhong Zhu, Wei Xia Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Wei XiaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86 27 8369 2651Email tjxiawei@hust.edu.cnPurpose: The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage.Methods: Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment.Results: Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes.Conclusion: CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.Keywords: copper nanoparticles, cytotoxicity, oxidative stress, heme oxygenase 1
format	article
author	Zou L Cheng G Xu C Liu H Wang Y Li N Fan X Zhu C Xia W
author_facet	Zou L Cheng G Xu C Liu H Wang Y Li N Fan X Zhu C Xia W
author_sort	Zou L
title	Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
title_short	Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
title_full	Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
title_fullStr	Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
title_full_unstemmed	Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies
title_sort	copper nanoparticles induce oxidative stress via the heme oxygenase 1 signaling pathway in vitro studies
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/521f1d9f5cd1434280961f2d2a66bb93
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Copper Nanoparticles Induce Oxidative Stress via the Heme Oxygenase 1 Signaling Pathway in vitro Studies

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