کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2581906 | 1130212 | 2010 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ES936 stimulates DNA synthesis in HeLa cells independently on NAD(P)H:quinone oxidoreductase 1 inhibition, through a mechanism involving p38 MAPK
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کلمات کلیدی
DCFH-DAFCSp38NQO12′,7′-dichlorodihydrofluorescein diacetate - 2 '، 7'-dichlorodihydrofluorescein diacetateHET - ITSmall interfering RNA - RNA تداخل کوچکROS - ROSsiRNA - siRNAfetal calf serum - سرم گوساله جنینHeLa cells - سلول های هلاDNA synthesis - سنتز DNAHydroethidine - هیدروتیدینReactive 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
![عکس صفحه اول مقاله: ES936 stimulates DNA synthesis in HeLa cells independently on NAD(P)H:quinone oxidoreductase 1 inhibition, through a mechanism involving p38 MAPK ES936 stimulates DNA synthesis in HeLa cells independently on NAD(P)H:quinone oxidoreductase 1 inhibition, through a mechanism involving p38 MAPK](/preview/png/2581906.png)
چکیده انگلیسی
The indolequinone ES936 (5-methoxy-1,2-dimethyl-3-[(4-nitrophenol)methyl]-indole-4,7-dione) is a potent mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1). Here, we report that ES936 significantly stimulated thymidine incorporation in sparse cultures of human adenocarcinoma HeLa cells, but was without effect in dense cultures. Stimulation of DNA synthesis was not related with a DNA repair response because an increase in thymidine incorporation was not observed in cells treated with 2,5 bis-[1-aziridyl]-1,4 benzoquinone, a well-established antitumor quinone that causes DNA damage. Conversely, it was related with an increase of cell growth. NQO1 inhibition was not involved in ES936 stimulation of DNA synthesis, because the same response was observed in cells where NQO1 expression had been knocked down by small interfering RNA. Stimulation of DNA synthesis was reverted by treatment with ambroxol, a SOD mimetic, and by pyruvate, an efficient peroxide scavenger, supporting the involvement of alterations in cellular redox state. Pharmacological inhibition of p38 with either SB203580 or PD169316 completely abolished ES936-stimulated DNA synthesis, indicating the requirement of p38 activity. This is the first report that demonstrates the existence of an ES936-sensitive system which is separate from NQO1, modulating the redox state and cell growth in HeLa cells through a p38-dependent mechanism. Our results show that the effect ES936 exerts on DNA synthesis may be either positive or negative depending on the cellular context and growth conditions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 186, Issue 2, 30 July 2010, Pages 174-183
Journal: Chemico-Biological Interactions - Volume 186, Issue 2, 30 July 2010, Pages 174-183
نویسندگان
David González-Aragón, Francisco J. AlcaÃn, Julia Ariza, Laura Jódar, Nuria Barbarroja, Chary López-Pedrera, José M. Villalba,