کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8539142 | 1561126 | 2017 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of histone acetylation in activation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway by manganese chloride
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کلمات کلیدی
TSANF-E2-related factor 2 (Nrf2)Nrf2GSHHO-1HRPPC12HDACROS - ROSHistone acetylation - استیلیت هیستونAnacardic acid - اسید آناکاردیکParkinson's disease - بیماری پارکینسونTrichostatin A - تریکوستاتین ANeurotoxicity - سمیت عصبیantioxidant response elements - عناصر پاسخ آنتی اکسیدانARE - هستندheme oxygenase 1 - همای اکسیژناز 1Histone acetyltransferase - هیستون استیل ترانسفرازhistone deacetylase - هیستون داستیلازHorseradish peroxidase - پراکسیداز هوررادیشreduced glutathione - کاهش گلوتاتیونHAT - کلاهmanganese chloride - کلرید منگنزReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Manganese neurotoxicity is characterized by Parkinson-like symptoms with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a good understanding of the mechanism of Parkinson's disease (PD). In this study, we first confirmed that MnCl2 can promote the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein in the nucleus or cytoplasm while increasing the binding activity of Nrf2 and antioxidant response elements, further promoting the expression of downstream target gene heme oxygenase 1 (HO-1) and leading to increase levels of reactive oxygen species (ROS) and reduce the levels of reduced glutathione (GSH). Second, we investigated the role of histone acetylation in the activation of Nrf2/HO-1 pathway by manganese chloride in rat adrenal pheochromocytoma (PC12) cells. Histone acetyltransferase inhibitor (anacardic acid) and histone deacetylase inhibitor (trichostatin A, TSA) were used as pretreatment reagents to adjust the level of histone acetylation. Here, we show that downregulation of histone acetylation can inhibit Mn-induced Nrf2 nuclear translocation and further inhibits the Mn-activated Nrf2/HO-1 pathway. This downregulation also promotes manganese-induced increase of ROS and decrease of GSH in neurons. These results suggest that the downregulation of histone acetylation may play an important role in the neurotoxicity caused by manganese and that TSA may provide new ideas and targets in treating manganese-induced Parkinson's syndrome and PD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 336, 1 December 2017, Pages 94-100
Journal: Toxicology and Applied Pharmacology - Volume 336, 1 December 2017, Pages 94-100
نویسندگان
Zhipeng Zhang, Zhenkun Guo, Yanting Zhan, Huangyuan Li, Siying Wu,