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Letters in Drug Design & Discovery

Author(s): Wioletta Ratajczak-Wrona* and Ewa Jablonska

DOI: 10.2174/1570180815666180426121503

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The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

Page: [194 - 199] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO).

Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern.

Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils.

Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Keywords: N-nitrosodimethylamine (NDMA), neutrophils, Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS), MAPK PI3K–Akt/PKB, JAK/STAT, AP1, NF-kB.

Graphical Abstract

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