Ulrich Forstermann

NO Synthesis and NOS Regulation

Of the three established NOS isozymes, nNOS and eNOS are low output, Ca2+-activated enzymes whose main physiological function is signal transduction. They usually show a constitutive, basal expression, which however, can be modified by various agents and conditions. In addition to the intracellular Ca2+ level, post-translational modifications and the subcellular targeting of these enzymes determine their activity. iNOS is a high output enzyme that can produce cytotoxic amounts of NO. iNOS is mainly regulated at the level of expression, with transcriptional, post-transcriptional and translational mechanisms involved. The stimuli and conditions that determine iNOS expression are cell- and species-specific. Once expressed, iNOS does not seem to be subject to any major regulation of its enzymatic activity. Thus, nature has invented a large array of regulatory mechanisms controlling the production of the pluripotent molecule NO.

Non-Vertebrate Nitric Oxide Synthases

NO is an important signalling molecule making essential contributions to innate immunity in mammals. Interestingly, also several non-vertebral NOS have been described. Aside from a role in the feeding of bloodsucking insects, NO has been shown, for example, to play an important role in Drosophila innate immunity …