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Title 

Cyclo(dehydrohistidyl-L-tryptophyl) inhibits nitric oxide production by preventing the dimerization of inducible nitric oxide synthase

Authors 

Mi Jin SohnG M HurH S ByunWon Gon Kim

Publisher 

Elsevier

Issue Date 

2008

Citation 

Biochemical Pharmacology, vol. 75, no. 4, pp. 923-930

Keywords 

BV-2 microgliacyclo(dehydrohistidyl-l-tryptophyl)dimerizationiNOSLPSnitric oxideinducible nitric oxide synthasenitric oxide synthase type II

Abstract 

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.

ISSN 

0006-2952

Link 

http://dx.doi.org/10.1016/j.bcp.2007.10.021

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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