PMID- 17316568 OWN - NLM STAT- MEDLINE DCOM- 20070508 LR - 20161124 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 355 IP - 3 DP - 2007 Apr 13 TI - A critical role for p38 map kinase in NF-kappaB signaling during intermittent hypoxia/reoxygenation. PG - 728-33 AB - NF-kappaB-dependent inflammatory gene expression is induced by intermittent hypoxia/reoxygenation (IHR), an event that we have hypothesized may contribute to the cardiovascular pathophysiology associated with obstructive sleep apnoea syndrome (OSAS). Here, we have investigated the cellular signaling mechanisms involved. Using an established endothelial cell in vitro model, we confirm a selective activation of the pro-inflammatory transcription factor NF-kappaB over the adaptive hypoxia-inducible factor-1 (HIF-1) in IHR-stimulated bovine aortic endothelial cells. IHR activates the I-kappaB kinase (IKK) complex, leading to phosphorylation/degradation of I-kappaB alpha. IHR activates p38 MAPK and pharmacological inhibition of p38 (using SB 203580, 10 microM) abolishes NF-kappaB activation by IHR. Furthermore, depletion of p38 using siRNA significantly reduces IHR-induced NF-kappaB activity. Thus, IHR activates NF-kappaB in an IKK-dependent manner signaled at least in part via activation of p38 MAPK. FAU - Ryan, Silke AU - Ryan S AD - School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. FAU - McNicholas, Walter T AU - McNicholas WT FAU - Taylor, Cormac T AU - Taylor CT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070209 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - S88TT14065 (Oxygen) SB - IM MH - Aerobiosis MH - Anaerobiosis MH - HeLa Cells MH - Humans MH - Hypoxia/*enzymology MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - I-kappa B Kinase/metabolism MH - NF-kappa B/*metabolism MH - Oxygen/metabolism MH - Phosphorylation MH - RNA, Small Interfering/pharmacology MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/*physiology EDAT- 2007/02/24 09:00 MHDA- 2007/05/09 09:00 CRDT- 2007/02/24 09:00 PHST- 2007/02/01 00:00 [received] PHST- 2007/02/03 00:00 [accepted] PHST- 2007/02/24 09:00 [pubmed] PHST- 2007/05/09 09:00 [medline] PHST- 2007/02/24 09:00 [entrez] AID - S0006-291X(07)00286-0 [pii] AID - 10.1016/j.bbrc.2007.02.015 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2007 Apr 13;355(3):728-33. doi: 10.1016/j.bbrc.2007.02.015. Epub 2007 Feb 9.