کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11030732 | 1646165 | 2018 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of NRF2 signaling and increased reactive oxygen species during embryogenesis in a rat model of retinoic acid-induced neural tube defects
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کلمات کلیدی
GSTsTXNRDGCLMGCLCNQO1Heme oxygenase-1GSSGGSHHO-1Nrf2keap1 - buy1ROS - ROSthioredoxin reductase - تریودوکسین ردوکتازOxidative stress - تنش اکسیداتیوRetinoic acid - رتینوئیک اسیدantioxidant response element - عنصر پاسخ آنتی اکسیدانnuclear factor erythroid 2-related factor 2 - فاکتور هسته ای عامل erythroid 2 مرتبط 2Neural tube defects - نقص لوله عصبیARE - هستندKelch-like ECH-associated protein 1 - پروتئین مرتبط با ECH کلچ 1reduced glutathione - کاهش گلوتاتیونGlutamate cysteine ligase catalytic subunit - کلوتامین کاتالیزوری لیستاز سیستئین گلوتاماتglutathione S-transferases - گلوتاتیون S-transferasesoxidized glutathione - گلوتاتیون اکسید شدهglutathione reductase - گلوتاتیون ردوکتازReactive 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
Exposure to retinoic acid (RA) during pregnancy increases the risk of serious neural tube defects (NTDs) in the developing fetus. The precise molecular mechanism for this process is unclear; however, RA is associated with oxidative stress mediated by reactive oxygen species. Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of oxidative stress that directs the expression of antioxidant genes and detoxifying proteins to maintain redox homeostasis. We established a rat model of NTDs in which pregnant dams were administered all-trans (at)RA on gestational day 10, and oxidative stress levels and the spatiotemporal expression of NRF2 and its downstream targets were examined in the resulting embryos and in maternal blood. In the NTD group, total antioxidative capacity decreased and 8-hydroxy-2â²-deoxyguanosine increased in maternal serum and fetal spinal cord tissues. Plasma GSH content, the GSH/GSSG ratio, and glutathione peroxidase activity in fetal spinal cords were lower in the NTD group relative to controls. We detected NRF2 protein reduction and concomitant upregulation of Kelch-like ECH-associated protein 1 (KEAP1) - a cytoplasmic inhibitor of NRF2 - in the NTD group. The mRNA and protein levels of downstream targets of NRF2 were downregulated in the spinal cords of NTD embryos. These data demonstrate substantial oxidative stress and NRF2 signaling pathway disruption in a model of NTDs induced by atRA. The inhibitory effects of atRA on NRF2 signaling may lower cellular defenses against RA-induced oxidative stress and could play important roles in NTD occurrence during embryonic development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 69, December 2018, Pages 84-92
Journal: NeuroToxicology - Volume 69, December 2018, Pages 84-92
نویسندگان
Dan Liu, Jia Xue, Yusi Liu, Hui Gu, Xiaowei Wei, Wei Ma, Wenting Luo, Ling Ma, Shanshan Jia, Naixuan Dong, Jieting Huang, Yanfu Wang, Zhengwei Yuan,