کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909528 1046729 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
pO2-dependent NO production determines OPPC activity in macrophages
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
pO2-dependent NO production determines OPPC activity in macrophages
چکیده انگلیسی

Stimulated macrophages produce nitric oxide (NO) via inducible nitric oxide synthase (iNOS) using molecular O2, L-arginine, and NADPH. Exposure of macrophages to hypoxia decreases NO production within seconds, suggesting substrate limitation as the mechanism. Conflicting data exist regarding the effect of pO2 on NADPH production via the oxidative pentose phosphate cycle (OPPC). Therefore, the present studies were developed to determine whether NADPH could be limiting for NO production under hypoxia. Production of NO metabolites (NOx) and OPPC activity by RAW 264.7 cells was significantly increased by stimulation with lipopolysaccharide (LPS) and interferon γ (IFNγ) at pO2 ranging from 0.07 to 50%. OPPC activity correlated linearly with NOx production at pO2 > 0.13%. Increased OPPC activity by stimulated RAW 264.7 cells was significantly reduced by 1400 W, an iNOS inhibitor. OPPC activity was significantly increased by concomitant treatment of stimulated RAW 264.7 cells with chemical oxidants such as hydroxyethyldisulfide or pimonidazole, at 0.07 and 50% O2, without decreasing NOx production. These results are the first to investigate the effect of pO2 on the relationship between NO production and OPPC activity, and to rule out limitations in OPPC activity as a mechanism by which NO production is decreased under hypoxia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 48, Issue 2, 15 January 2010, Pages 189–195
نویسندگان
, , , ,