دانلود مقاله ISI انگلیسی شماره 106535
ترجمه فارسی عنوان مقاله

مهار تیمیدیلات سنتاز بر رشد لوله عصبی در موش نقش دارد

عنوان انگلیسی
Inhibition of thymidylate synthase affects neural tube development in mice
کد مقاله سال انتشار تعداد صفحات مقاله انگلیسی
106535 2018 9 صفحه PDF
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : Reproductive Toxicology, Volume 76, March 2018, Pages 17-25

پیش نمایش مقاله
پیش نمایش مقاله  مهار تیمیدیلات سنتاز بر رشد لوله عصبی در موش نقش دارد

چکیده انگلیسی

Thymidylate synthase (TYMS) is a key enzyme in the de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP) from 2′-deoxyuridine-5′-monophosphate (dUMP). Our aim was to investigate the role of dTMP dysmetabolism via inhibition of TYMS by an inhibitor, 5-fluorouracil (5-FU) in the occurrence of neural tube defects (NTDs). We found that a high incidence of NTDs occurred after treatment with 5-FU at 12.5 mg/kg body weight. TYMS activity was significantly inhibited with decreased dTMP and accumulation of dUMP after 5-FU injection. The proliferation of neuroepithelial cells were markedly inhibited in NTDs compared with control. Expressions of proliferating cell nuclear antigen and phosphohistone H3 were significantly decreased in NTDs, while phosphorylated replication protein A2, P53 and Caspase3 were significantly increased in NTDs compared with control. These results indicated that inhibition of TYMS affected the balance between proliferation and apoptosis in neuroepithelial cells, which might shed some lights on the mechanisms involved in NTDs.