Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system

Shefang Ye,1 Min Chen,1 Yuanqin Jiang,1,2 Mingliang Chen,3 Tong Zhou,1 Yange Wang,1 Zhenqing Hou,1 Lei Ren11Department of Biomaterials, Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, People's Republic of China; 2First Affiliated Hospital of Xiame...

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Autores principales:	Ye SF, Chen M, Jiang YQ, Chen ML, Zhou T, Wang YG, Hou ZQ, Ren L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/57fdf04767434d95b927ea4052a3ce80
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spelling	oai:doaj.org-article:57fdf04767434d95b927ea4052a3ce802021-12-02T02:01:33ZPolyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system1178-2013https://doaj.org/article/57fdf04767434d95b927ea4052a3ce802014-04-01T00:00:00Zhttp://www.dovepress.com/polyhydroxylated-fullerene-attenuates-oxidative-stress-induced-apoptos-a16619https://doaj.org/toc/1178-2013 Shefang Ye,1 Min Chen,1 Yuanqin Jiang,1,2 Mingliang Chen,3 Tong Zhou,1 Yange Wang,1 Zhenqing Hou,1 Lei Ren11Department of Biomaterials, Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, People's Republic of China; 2First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China; 3Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, People's Republic of ChinaAbstract: Polyhydroxylated derivatives of fullerene C60, named fullerenols (C60[OH]n), have stimulated great interest because of their potent antioxidant properties in various chemical and biological systems, which enable them to be used as a new promising pharmaceutical for the future treatment of oxidative stress-related diseases, but the details remain unknown. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a principal transcription factor that regulates expression of several antioxidant genes via binding to the antioxidant response element and plays a crucial role in cellular defence against oxidative stress. In this study we investigated whether activation of the Nrf2/antioxidant response element pathway contributes to the cytoprotective effects of C60(OH)24. Our results showed that C60(OH)24 enhanced nuclear translocation of Nrf2 and upregulated expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1, and γ-glutamate cysteine ligase in A549 cells. Treatment with C60(OH)24 resulted in phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK), extracellular signal-regulated kinases, and c-Jun-N-terminal kinases. By using inhibitors of cellular kinases, we showed that pretreatment of A549 cells with SB203580, a specific inhibitor of p38 MAPK, abolished nuclear translocation of Nrf2 and induction of HO-1 protein induced by C60(OH)24, indicating an involvement of p38 MAPK in Nrf2/HO-1 activation by C60(OH)24. Furthermore, pretreatment with C60(OH)24 attenuated hydrogen peroxide-induced apoptotic cell death in A549 cells, and knockdown of Nrf2 by small interfering ribonucleic acid diminished C60(OH)24-mediated cytoprotection. Taken together, these findings demonstrate that C60(OH)24 may attenuate oxidative stress-induced apoptosis via augmentation of Nrf2-regulated cellular antioxidant capacity, thus providing insights into the mechanisms of the antioxidant properties of C60(OH)24.Keywords: fullerenol, Nrf2, oxidative stress, cytoprotection, A549 cellsYe SFChen MJiang YQChen MLZhou TWang YGHou ZQRen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2073-2087 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ye SF Chen M Jiang YQ Chen ML Zhou T Wang YG Hou ZQ Ren L Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
description	Shefang Ye,1 Min Chen,1 Yuanqin Jiang,1,2 Mingliang Chen,3 Tong Zhou,1 Yange Wang,1 Zhenqing Hou,1 Lei Ren11Department of Biomaterials, Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, People's Republic of China; 2First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China; 3Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, People's Republic of ChinaAbstract: Polyhydroxylated derivatives of fullerene C60, named fullerenols (C60[OH]n), have stimulated great interest because of their potent antioxidant properties in various chemical and biological systems, which enable them to be used as a new promising pharmaceutical for the future treatment of oxidative stress-related diseases, but the details remain unknown. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a principal transcription factor that regulates expression of several antioxidant genes via binding to the antioxidant response element and plays a crucial role in cellular defence against oxidative stress. In this study we investigated whether activation of the Nrf2/antioxidant response element pathway contributes to the cytoprotective effects of C60(OH)24. Our results showed that C60(OH)24 enhanced nuclear translocation of Nrf2 and upregulated expression of phase II antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1, and γ-glutamate cysteine ligase in A549 cells. Treatment with C60(OH)24 resulted in phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK), extracellular signal-regulated kinases, and c-Jun-N-terminal kinases. By using inhibitors of cellular kinases, we showed that pretreatment of A549 cells with SB203580, a specific inhibitor of p38 MAPK, abolished nuclear translocation of Nrf2 and induction of HO-1 protein induced by C60(OH)24, indicating an involvement of p38 MAPK in Nrf2/HO-1 activation by C60(OH)24. Furthermore, pretreatment with C60(OH)24 attenuated hydrogen peroxide-induced apoptotic cell death in A549 cells, and knockdown of Nrf2 by small interfering ribonucleic acid diminished C60(OH)24-mediated cytoprotection. Taken together, these findings demonstrate that C60(OH)24 may attenuate oxidative stress-induced apoptosis via augmentation of Nrf2-regulated cellular antioxidant capacity, thus providing insights into the mechanisms of the antioxidant properties of C60(OH)24.Keywords: fullerenol, Nrf2, oxidative stress, cytoprotection, A549 cells
format	article
author	Ye SF Chen M Jiang YQ Chen ML Zhou T Wang YG Hou ZQ Ren L
author_facet	Ye SF Chen M Jiang YQ Chen ML Zhou T Wang YG Hou ZQ Ren L
author_sort	Ye SF
title	Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
title_short	Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
title_full	Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
title_fullStr	Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
title_full_unstemmed	Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system
title_sort	polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying nrf2-regulated cellular antioxidant defence system
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/57fdf04767434d95b927ea4052a3ce80
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Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence system

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