caa a22 4500 445852801 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-011-0709-y doi (NATIONALLICENCE)springer-10.1007/s00204-011-0709-y Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway [Elektronische Daten] [Cheng Yen, Tsung Ho, Chin Wu, Chun Chang, Chin Su, Ya Chen, Tzyy Jinn, Tien Lu, Po Cheng, Yi Su, Shing Liu, Chun Huang] Arsenic pollution is a major public health problem worldwide. Inorganic arsenic (iAs) is usually more harmful than organic ones. iAs pollution increases the risk of human diseases such as peripheral vascular disease and cancer. However, the toxicological effects of iAs in the brain are mostly unclear. Here, we investigated the toxic effects and possible mechanisms of iAs in the cerebrum of mice after exposure to iAs (0.5 and 5ppm (mg/l) As2O3, via the drinking water), which was the possible human exposed dose via the ingestion in iAs-contaminated areas, for 6consecutive weeks. iAs dose-dependently caused an increase of LPO production in the plasma and cerebral cortex. iAs also decreased the reduced glutathione levels and the expressions of NQO1 and GPx mRNA in the cerebral cortex. These impairments in the cerebral cortex caused by iAs exposure were significantly correlated with the accumulation of As. Moreover, iAs induced the production of apoptotic cells and activation of caspase-3, up-regulation of Bax and Bak, and down-regulation of Mcl-1 in the cerebral cortex. Exposure to iAs also triggered the expression of ER stress-related genes, including GRP78, GRP94, and CHOP. Meanwhile, an increase of p38 activation and dephosphorylation of ERK1/2 were shown in the cerebral cortex as a result of iAs-exposed mice. These iAs-induced damages and apoptosis-related signals could be significantly reversed by NAC. Taken together, these results suggest that iAs-induced oxidative stress causes cellular apoptosis in the cerebrum, signaling of p38 and ERK1/2, and ER stress may be involved in iAs-induced cerebral toxicity. Springer-Verlag, 2011 Inorganic arsenic nationallicence Apoptosis nationallicence Oxidative stress nationallicence ER stress nationallicence p38 nationallicence ERK1/2 nationallicence LPO : Lipid peroxidation nationallicence GSH : Glutathione nationallicence NQO1 : NAD(P)H: quinone oxidoreductase-1 nationallicence GPx : Glutathione peroxidase nationallicence Bax : Bcl-associated X protein nationallicence Bak : Bcl-2 homologous antagonist killer nationallicence Mcl-1 : Myeloid cell leukemia sequence 1 nationallicence ER : Endoplasmic reticulum nationallicence GRP : Glucose-regulated protein nationallicence CHOP : C/EBP homologous protein nationallicence ERK : Extracellular signal-regulated kinase nationallicence NAC : N-acetylcysteine nationallicence ROS : Reactive oxygen species nationallicence MDA : Malondiadehyde nationallicence Yen Cheng Department of Occupational Safety and Health, College of Health Care and Management, Chung Shan Medical University, No. 110, Sec. 1, Jian-Guo N. Rd., 40201, Taichung, Taiwan aut Ho Tsung School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Wu Chin Department of Public Health, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Chang Chun Department of Chinese Medicine, Chiayi Hospital, No. 312 Bei-gang Rd., 60096, Chiayi, Taiwan aut Su Chin Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., 50072, Changhua City, Changhua County, Taiwan aut Chen Ya Department of Physiology and Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Jinn Tzyy School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Lu Tien Graduate Institute of Drug Safety, College of Pharmacy, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Cheng Po Department of Otolaryngology, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nan-Ya S. Rd., Banciao Dist., 22060, New Taipei City, Taiwan aut Su Yi School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Liu Shing Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Rd., 10051, Taipei, Taiwan aut Huang Chun School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 565-575 0340-5761 85:6<565 2011 85 204 https://doi.org/10.1007/s00204-011-0709-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0709-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yen Cheng Department of Occupational Safety and Health, College of Health Care and Management, Chung Shan Medical University, No. 110, Sec. 1, Jian-Guo N. Rd., 40201, Taichung, Taiwan aut NATIONALLICENCE 700 1- Ho Tsung School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Wu Chin Department of Public Health, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Chang Chun Department of Chinese Medicine, Chiayi Hospital, No. 312 Bei-gang Rd., 60096, Chiayi, Taiwan aut NATIONALLICENCE 700 1- Su Chin Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., 50072, Changhua City, Changhua County, Taiwan aut NATIONALLICENCE 700 1- Chen Ya Department of Physiology and Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Jinn Tzyy School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Lu Tien Graduate Institute of Drug Safety, College of Pharmacy, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Cheng Po Department of Otolaryngology, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nan-Ya S. Rd., Banciao Dist., 22060, New Taipei City, Taiwan aut NATIONALLICENCE 700 1- Su Yi School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 700 1- Liu Shing Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Rd., 10051, Taipei, Taiwan aut NATIONALLICENCE 700 1- Huang Chun School of Chinese Medicine, College of Chinese Medicine, China Medical University, No. 91 Hsueh-Shih Rd., 40402, Taichung, Taiwan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 565-575 0340-5761 85:6<565 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer