کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10835165 1066044 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modeling gas phase nitric oxide release in lung epithelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Modeling gas phase nitric oxide release in lung epithelial cells
چکیده انگلیسی
Nitric oxide (NO) is present in exhaled breath and is generally considered to be a noninvasive marker of airway inflammation, and is thus of particular relevance to monitoring asthma. NO is produced when l-arginine is converted to l-citrulline by NO synthase (NOS); however, l-arginine is also the substrate for arginase and both enzymes are upregulated in asthma. Recent reports have speculated that enhanced expression of one or both enzymes could lead to a limitation in substrate availability, and hence impact downstream targets or markers such as exhaled NO. The non-linear nature and vastly different kinetics of the enzymes make predictions difficult, particularly over the wide range of enzyme activity between baseline and inflammation. In this study, we developed a steady state model of l-arginine transmembrane transport, NO production, diffusion, and gas phase NO release from lung epithelial cells. We validated our model with experimental results of gas phase NO release and intracellular l-arginine concentration in A549 cells, and then performed a sensitivity analysis to determine relative impact of each enzyme on NO production. Our model predicts intracellular l-arginine and gas phase NO release over a wide range of initial extracellular l-arginine concentrations following stimulation with cytomix (10 ng/ml TNF-α, IL-1β, and INF-γ). Relative sensitivity analysis demonstrates that enhanced arginase activity has little impact on l-arginine bioavailability for NOS. In addition, NOS activity is the dominant parameter which impacts gas phase NO release.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nitric Oxide - Volume 25, Issue 3, 30 October 2011, Pages 275-281
نویسندگان
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