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 Xiamen...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2014-04-01
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| Series: | International Journal of Nanomedicine |
| Online Access: | http://www.dovepress.com/polyhydroxylated-fullerene-attenuates-oxidative-stress-induced-apoptos-a16619 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-14T09:13:41Z |
| format | Article |
| id | doaj.art-57fdf04767434d95b927ea4052a3ce80 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-14T09:13:41Z |
| publishDate | 2014-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-57fdf04767434d95b927ea4052a3ce802022-12-21T23:08:30ZengDove Medical PressInternational Journal of Nanomedicine1178-20132014-04-012014Issue 12073208716619Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated cellular antioxidant defence systemYe SFChen MJiang YQChen MLZhou TWang YGHou ZQRen LShefang 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 cellshttp://www.dovepress.com/polyhydroxylated-fullerene-attenuates-oxidative-stress-induced-apoptos-a16619 |
| spellingShingle | 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 International Journal of Nanomedicine |
| title | 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_short | 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 |
| url | http://www.dovepress.com/polyhydroxylated-fullerene-attenuates-oxidative-stress-induced-apoptos-a16619 |
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