PMID- 19249125 OWN - NLM STAT- MEDLINE DCOM- 20091013 LR - 20171116 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 214 IP - 8 DP - 2009 TI - Effect of nitric oxide donors on NADPH oxidase signaling pathway in human neutrophils in vitro. PG - 692-702 LID - 10.1016/j.imbio.2008.12.001 [doi] AB - The production of reactive oxygen species (ROS) in activated neutrophils is catalyzed by NADPH oxidase, a multiproteins complex. Various protein kinases including protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) are involved in NADPH oxidase phosphorylation and activation. The main step in the NADPH oxidase activation is phosphorylation of its cytosolic protein p47(phox). We found previously that nitric oxide (NO) donors such as metabolite of molsidomine-SIN-1 and diethylamine/NO significantly impaired the ROS production in activated human neutrophils. In this study, we investigated the effects of both NO donors on NADPH oxidase-linked signaling proteins in activated neutrophils. We found that NO donors decreased the phosphorylation of p47(phox) on tyrosine and serine/threonine residues and PKC on serine residues in neutrophils. Both NO donors did not affect the phosphorylation of MAPKs. NO donors partially but significantly lost their ability to reduce ROS production in the presence of PKC but not MAPKs inhibitors. We show that whereas NO donors have no effect on MAPKs activity, they do decrease PMA- and/or fMLP-induced phosphorylation of p47(phox) and PKC as well as PMA- and fMLP-induced ROS production. FAU - Klink, Magdalena AU - Klink M AD - Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. mklink@cbm.pan.pl FAU - Jastrzembska, Katarzyna AU - Jastrzembska K FAU - Bednarska, Katarzyna AU - Bednarska K FAU - Banasik, Malgorzata AU - Banasik M FAU - Sulowska, Zofia AU - Sulowska Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090226 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Diethylamines) RN - 0 (Nitric Oxide Donors) RN - 31C4KY9ESH (Nitric Oxide) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 5O5U71P6VQ (linsidomine) RN - D46583G77X (Molsidomine) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 1.6.3.1 (neutrophil cytosolic factor 1) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Diethylamines/immunology/metabolism MH - Enzyme Activation MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Humans MH - Molsidomine/*analogs & derivatives/*antagonists & inhibitors/pharmacology MH - N-Formylmethionine Leucyl-Phenylalanine/immunology/metabolism MH - NADPH Oxidases/immunology/*metabolism MH - Neutrophils MH - Nitric Oxide/*metabolism MH - Nitric Oxide Donors/*pharmacology MH - Phosphorylation/drug effects/immunology MH - Protein Kinase C/metabolism MH - *Signal Transduction/drug effects/immunology MH - Substrate Specificity EDAT- 2009/03/03 09:00 MHDA- 2009/10/14 06:00 CRDT- 2009/03/03 09:00 PHST- 2008/07/14 00:00 [received] PHST- 2008/12/05 00:00 [revised] PHST- 2008/12/08 00:00 [accepted] PHST- 2009/03/03 09:00 [entrez] PHST- 2009/03/03 09:00 [pubmed] PHST- 2009/10/14 06:00 [medline] AID - S0171-2985(08)00163-0 [pii] AID - 10.1016/j.imbio.2008.12.001 [doi] PST - ppublish SO - Immunobiology. 2009;214(8):692-702. doi: 10.1016/j.imbio.2008.12.001. Epub 2009 Feb 26.