کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10768654 1050813 2005 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells
چکیده انگلیسی
Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD+, resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD+ pool, and of NAD+-dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD+ levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzyme inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 338, Issue 4, 30 December 2005, Pages 1805-1810
نویسندگان
, , , , , ,