کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2583733 1130701 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activation of neuronal nitric oxide synthase (nNOS) signaling pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Activation of neuronal nitric oxide synthase (nNOS) signaling pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced neurotoxicity
چکیده انگلیسی


• TCDD induced a time- and dose-dependent increase of nNOS in PC12 cells.
• TCDD induced apoptotic cell death in PC12 cells.
• Inhibition of nNOS blocked TCDD-induced neural apoptosis.
• In the brain cortex of SD rats, nNOS was associated with TCDD-induced neuronal apoptosis.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Environmental Toxicology and Pharmacology - Volume 38, Issue 1, July 2014, Pages 119–130
نویسندگان
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