caa a22 4500 445853743 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00204-010-0625-6 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0625-6 NF-E2-related factor 2 activation in PC12 cells: its protective role in manganese-induced damage [Elektronische Daten] [Huangyuan Li, Siying Wu, Nian Shi, Wei Lin, Junyi You, Wenhua Zhou] Manganese neurotoxicity presents with Parkinson-like symptoms that are associated with the generation of reactive oxygen species. Thus, its occurrence and severity can be reduced by cellular antioxidants. The components of the transcription factor NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway are the central regulators of cellular antioxidant responses. In this study, we investigated the role of activation of Nrf2 in response to oxidative damage induced by manganese chloride (MnCl2) in rat adrenal pheochromocytoma (PC12) cells. Exposure of PC12 cells to MnCl2 for 24h promoted an increased cytosolic and nuclear accumulation of Nrf2 and enhanced the binding of Nrf2 to the HO-1 gene ARE, thereby inducing the expression of an Nrf2-regulated gene, HO-1. Pre-treatment with tert-butylhydroquinone (tBHQ), a known agent that activates the Nrf2/ARE-HO-1 pathway, for 16h prior to the 24h MnCl2 exposure attenuated both the cytotoxicity and the apoptosis induced by MnCl2. These protective effects of tBHQ indicated a protective role for Nrf2 against MnCl2-induced cell damage. Taken together, these findings suggest that Nrf2 may play an important role in the protection of PC12 cells against MnCl2 neurotoxicity. Springer-Verlag, 2010 NF-E2-related factor 2 (Nrf2) nationallicence Heme oxygenase-1 (HO-1) nationallicence Apoptosis nationallicence Manganese chloride nationallicence tert-Butylhydroquinone (tBHQ) nationallicence Li Huangyuan Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut Wu Siying Department of Epidemiology and Health Statistics, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut Shi Nian Department of Health Toxicology, MOE Key lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China aut Lin Wei Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut You Junyi Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut Zhou Wenhua Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 901-910 0340-5761 85:8<901 2011 85 204 https://doi.org/10.1007/s00204-010-0625-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0625-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Huangyuan Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut NATIONALLICENCE 700 1- Wu Siying Department of Epidemiology and Health Statistics, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut NATIONALLICENCE 700 1- Shi Nian Department of Health Toxicology, MOE Key lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China aut NATIONALLICENCE 700 1- Lin Wei Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut NATIONALLICENCE 700 1- You Junyi Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut NATIONALLICENCE 700 1- Zhou Wenhua Department of Occupational and Environmental Health, Research Unit for Toxicology and Chemical Safety Assessment, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Jiaotong Road No. 88, 350004, Fuzhou, China aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 901-910 0340-5761 85:8<901 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer