期刊
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
卷 38, 期 1, 页码 119-130出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2014.05.003
关键词
nNOS; Apoptosis; PC12 cells; TCDD
资金
- National Natural Science Foundation of China [21077061, 21277078]
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, TODD 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 TODD-induced neuronal apoptosis. Together, our findings establish a role for nNOS as an enhancer of TODD-induced apoptosis in PC12 cells. (C) 2014 Elsevier B.V. All rights reserved.
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