title: Activation of neuronal nitric oxide synthase (nNOS) signaling pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been reported to cause alterations in cognitive and motor behavior during both development and adulthood. In this study, the neuronal nitric oxide synthase (nNOS) signaling pathway was investigated in differentiated pheochromocytoma (PC12) cells to better understand the mechanisms of TCDD-induced neurotoxicity. TCDD exposure induced a time- and dose-dependent increase in nNOS expression. High levels of nitric oxide (NO) production by nNOS activation induced mitochondrial cytochrome c (Cyt-c) release and down-regulation of Bcl-2. Additionally, TCDD increased the expression of active caspase-3 and significantly led to apoptosis in PC12 cells. However, these effects above could be effectively inhibited by the addition of 7-nitroindazole (7-NI), a highly selective nNOS inhibitor. Moreover, in the brain cortex of Sprague-Dawley (SD) rats, nNOS was also found to have certain relationship with TCDD-induced neuronal apoptosis. Together, our findings establish a role for nNOS as an enhancer of TCDD-induced apoptosis in PC12 cells.
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Junkang
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Xi
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Aihong
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Aisong
authors.initials: A
authors.lastname: Guo
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Shengyang
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China.
authors.forename: Jianya
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226001 Jiangsu, People's Republic of China. Electronic address: chengangjp2002@yahoo.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D016716:PC12 Cells; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004785:Environmental Pollutants; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009498:Neurotoxins; D000072317:Polychlorinated Dibenzodioxins; D019253:Proto-Oncogene Proteins c-bcl-2; D009569:Nitric Oxide; D045304:Cytochromes c; D052248:Nitric Oxide Synthase Type I
keywords: Apoptosis; PC12 cells; TCDD; nNOS