Post-translational Regulation of High Output NO and Endothelial Barrier Dysfuncti

$345,118P01FY2011HLNIH

University Of Illinois At Chicago, Chicago IL

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Abstract

The major source of "high-output" nitric oxide (NO) during inflannmatton is inducible NO synthase (iNOS). Although iNOS is a transcriptionally-regulated generator of high NO, we have discovered a novel mode of post- translational, G protein coupled receptor (GPCR)-mediated activation of iNOS via ERK-dependent phosphorylation in endothelial cells. Post-translational activation of INOS results in a further 3- to 5-fold increase in NO concentration over its already high basal amount. In

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