کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1924831 1536317 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glutathione modifies the oxidation products of 2′-deoxyguanosine by singlet molecular oxygen
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Glutathione modifies the oxidation products of 2′-deoxyguanosine by singlet molecular oxygen
چکیده انگلیسی


• GSH, not GSSG, increases 8-oxodGuo generation by favoring the reduction of 8-OOHdGuo.
• GSH and GSSG do not act directly in generation of dSp by 1O2 oxidation of 8-oxodGuo.
• GSSG is more effective than GSH as 1O2 physical quencher in dGuo oxidation.

The oxidation of the free nucleoside 2′-deoxyguanosine (dGuo) by singlet molecular oxygen (1O2) has been studied over the three last decades due to the major role of DNA oxidation products in process such as ageing, mutation and carcinogenesis. In the present work we investigated the dGuo oxidation by 1O2 in the presence of the important low molecular antioxidant, glutathione, in its reduced (GSH) and oxidized (GSSG) forms. There were applied different conditions of concentration, pH, time of incubation, and the use of a [18O]-labeled thermolabile endoperoxide naphthalene derivative as a source of [18O]-labeled 1O2. Data was obtained through high performance liquid chromatography (HPLC) and HPLC coupled to micrOTOF Q-II analysis of the main oxidation products: the diastereomers of spiroiminodihydantoin-2′-deoxyribonucleosides (dSp) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). An intriguing result was that 8-oxodGuo levels increased by 100 fold when dGuo was oxidized by 1O2 in the presence of GSH and by 2 fold in the presence of GSSG, while dSp levels dropped to zero for both conditions. All data from dGuo, 8-oxodGuo and dSp quantification together with the analysis of residual GSH/GSSG content in each sample strongly suggest that glutathione modifies the mechanism of dGuo oxidation by 1O2 by disfavoring the pathway of dSp formation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 586, 15 November 2015, Pages 33–44
نویسندگان
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