Nitric Oxide

Nitric Oxide (Second Edition)

Biology and Pathobiology
2010, Pages 211-267
Nitric Oxide

Chapter 7 - Regulation of the Expression of Inducible Nitric Oxide Synthase

https://doi.org/10.1016/B978-0-12-373866-0.00007-1Get rights and content

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This chapter reveals how nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) exerts multiple beneficial microbicidal, antiviral, antiparasital, complex immunomodulatory, and antitumoral effects. Aberrant iNOS induction in the wrong place or at the wrong time has detrimental consequences and it is involved in the pathophysiology of several human diseases. Therefore, iNOS has to be regulated very tightly. The inducible isoform of NOS is mainly regulated at the level of expression. The mechanisms regulating iNOS expression involve modulation of promoter activity, mRNA stability and translatability, and protein stability. Modulation of iNOS expression is the major regulation mechanism for iNOS. Both transcriptional and post-transcriptional mechanisms have been shown to regulate iNOS expression. In contrast to the murine system, induction of human iNOS expression normally needs a complex mixture of cytokines. Pathways resulting in the induction of iNOS expression vary in different cells or species. Activation of the transcription factors NF-kB and STAT-1α and thereby activation of the iNOS promoter seems to be an essential step for iNOS induction in most human cells. However, at least in the human system, post-transcriptional mechanisms, involving a complex network of RNA binding proteins built up by AUF1, HuR, KSRP, PTB, and TTP, are also critically involved in the regulation of iNOS expression.

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