کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5855042 | 1562057 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
2,3,7,8-TCDD induces neurotoxicity and neuronal apoptosis in the rat brain cortex and PC12 cell line through the down-regulation of the Wnt/β-catenin signaling pathway
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کلمات کلیدی
LiClp-GSK-3βrat pheochromocytomaPC12ARNTCCK-8GSK-3βTCDDAHR2,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسینNeuronal apoptosis - آپوپتوز عصبیaryl hydrocarbon receptor nuclear translocator - اتمسفر هسته ای گیرنده آرویل کربنTUNEL - تونلCNS - دستگاه عصبی مرکزیRoom temperature - دمای اتاقPC12 cell - سلول PC12Neurotoxicity - سمیت عصبیcentral nervous system - سیستم عصبی مرکزیWnt/β-catenin signaling - سیگنال Wnt / β-cateninphospho-glycogen synthase kinase-3β - فسفو گلیکوژن سنتاز کیناز 3βRat brain cortex - قشر مغز موشlithium chloride - لیتیم کلریدGlycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3βaromatic hydrocarbon receptor - گیرنده هیدروکربن معطر
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
TCDD exposure has various toxic effects on in the human nervous system resulting in various developmental and behavioral deficits. However the underlying molecular mechanism of TCDD-induced adverse effects on the CNS and associated signaling pathways remains largely unknown. Herein we analyzed acute TCDD exposure in the rat brain cortex to investigate whether misregulation of the Wnt/β-catenin signaling pathway plays a role in neurotoxicity. Western blot and immunohistochemical experiments revealed a significant down-regulation of β-catenin and phospho-glycogen synthase kinase-3β (pSer9-GSK-3β) after TCDD exposure. TUNEL assay results showed apoptosis occurs mainly at day 7 after TCDD treatment. Immunofluorescent labeling indicated that β-catenin was localized mainly in the neurons; co-localization of β-catenin and active caspase-3 was found following TCDD exposure. Further, TCDD exposure decreased the level of pSer9-GSK-3β and β-catenin, and increased apoptosis in the PC12 neuronal cell line in a dose-dependent manner. Interestingly the application of lithium chloride, a GSK-3β inhibitor, reversed the suppressive effect of TCDD on β-catenin in PC12 cells and primary cortical neurons restoring cell viability and protecting cells from apoptosis as compared to untreated controls. Taken together, these results indicate that the canonical Wnt/β-catenin signaling pathway may play an important role in TCDD-induced neurotoxicity and neuronal apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 37, July 2013, Pages 63-73
Journal: NeuroToxicology - Volume 37, July 2013, Pages 63-73
نویسندگان
Guangfei Xu, Qiang Zhou, Chunhua Wan, Ying Wang, Jiao Liu, Yuanye Li, Xiaoke Nie, Chun Cheng, Gang Chen,