کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5824259 | 1118471 | 2008 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cyclo(dehydrohistidyl-l-tryptophyl) inhibits nitric oxide production by preventing the dimerization of inducible nitric oxide synthase
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کلمات کلیدی
guanosine-3′,5′-cyclic monophosphateGTPBV-2 microgliaNG-nitro-l-arginine methyl estercGMPiNOSHUVECLPSeNOSnNOSl-NAME - L-NAMEDimerization - اندازه گیریHuman umbilical vein endothelial cells - سلول های اندوتلیالی ورید ناف انسانinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییendothelial nitric oxide synthase - سنتاز اکسید نیتریک اندوتلیالneuronal nitric oxide synthase - سنتاز اکسید نیتریک عصبیlipopolysaccharide - لیپوپلی ساکاریدNitric oxide - نیتریک اکسیدGuanosine triphosphate - گوانوزین تری فسفات
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Dimerization of inducible NOS has been known to be a potential therapeutic target for iNOS-mediated pathologies. Cyclic dipeptides are among the simplest peptides commonly found as by-products of food processing or metabolites of microorganisms. In this study, we found that cyclo(dehydrohistidyl-l-tryptophyl) (CDHT), a cyclic dipeptide from an unidentified fungal strain Fb956, prevents iNOS dimerization in activated microglial BV-2 cells. CDHT inhibited NO production with an IC50 of 6.5 μM in LPS-treated BV-2 cells. Western blot analysis and iNOS activity measurement of fractions from size-exclusion chromatography of cell lysates indicated that CDHT inhibits dimerization of iNOS, while it has no effect on iNOS expression or enzyme activity. The CDHT inhibition of iNOS dimerization was confirmed by partially denaturing SDS-PAGE analysis. In contrast, CDHT did not affect cGMP production in endothelial HUVEC cells, which indicates no inhibition of endothelial NOS activity. These results reveal that CDHT, one of the simplest and cyclic dipeptides, selectively inhibits NO production by inhibiting iNOS dimerization, and could be a useful therapeutic agent for inflammation-mediated diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 75, Issue 4, 15 February 2008, Pages 923-930
Journal: Biochemical Pharmacology - Volume 75, Issue 4, 15 February 2008, Pages 923-930
نویسندگان
Mi-Jin Sohn, Gang-Min Hur, Hee-Sun Byun, Won-Gon Kim,