PMID- 24535078
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20140226
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 9
IP  - 4
DP  - 2014 Apr
TI  - Propofol selectively inhibits nuclear factor-kappaB activity by suppressing p38 
      mitogen-activated protein kinase signaling in human EA.hy926 endothelial cells 
      during intermittent hypoxia/reoxygenation.
PG  - 1460-6
LID - 10.3892/mmr.2014.1946 [doi]
AB  - Intermittent hypoxia/reoxygenation (IHR) induces proinflammatory cytokines, 
      contributing to the pathogenic process of atherosclerosis associated with 
      obstructive sleep apnea (OSA). Two transcription factors, nuclear factor-kappaB 
      (NF-kappaB) and hypoxia-inducible factor-1 (HIF-1), have been indicated to mediate 
      proinflammatory cytokines during IHR. The anti-inflammatory effects of propofol 
      have attracted increasing attention in regard to the treament of multiple 
      diseases associated with inflammation. The present study examined whether 
      propofol inhibits NF-kappaB and HIF-1 activity in vascular endothelial cells during 
      IHR. EA.hy926 endothelial cells were exposed to IHR for 64 cycles with or without 
      propofol treatment. Gene knockdown by transfection of siRNA against p38 
      mitogen-activated protein kinase (MAPK) was also used to investigate the 
      molecular mechanisms. Compared with the control group, IHR exposure significantly 
      induced the activation of NF-kappaB and HIF-1, enhanced the mRNA expression of 
      proinflammatory cytokines and increased the activation of p38 MAPK. Propofol 
      dose-dependently inhibited the IHR‑induced activation of NF-kappaB, but did not 
      change the activation of HIF-1, which was accompanied by decreased levels of 
      proinflammatory cytokines. In addition, IHR‑induced p38 MAPK activity was 
      attenuated by propofol in a similar manner to the reduction in NF-kappaB activity. 
      Furthermore, knockdown of p38 MAPK with siRNA significantly reduced the 
      IHR‑induced activation of NF-kappaB, while not affecting HIF-1. These data 
      demonstrate that propofol selectively attenuates the IHR‑induced activation of 
      NF-kappaB, but not HIF-1, in vascular endothelial cells, and these beneficial effects 
      are likely to be based on the inhibition of the p38 MAPK signaling pathway. 
      Propofol may have the potential to prevent atherosclerosis in patients with OSA 
      by inhibiting NF-kappaB‑mediated inflammation in the vascular endothelium.
FAU - Li, Dongliang
AU  - Li D
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 
      250012, P.R. China.
FAU - Wang, Chunling
AU  - Wang C
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 
      250012, P.R. China.
FAU - Li, Ning
AU  - Li N
AD  - School of Public Health, Jining Medical University, Jining, Shandong 272067, P.R. 
      China.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 
      250012, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140211
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Cytokines)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - S88TT14065 (Oxygen)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Blotting, Western
MH  - Cell Hypoxia/drug effects
MH  - Cytokines/metabolism
MH  - Endothelial Cells/drug effects/enzymology
MH  - Genes, Reporter
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Luciferases/metabolism
MH  - NF-kappa B/*metabolism
MH  - Oxygen/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Propofol/*pharmacology
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction/*drug effects
MH  - Transfection
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2014/02/19 06:00
MHDA- 2014/10/22 06:00
CRDT- 2014/02/19 06:00
PHST- 2013/06/12 00:00 [received]
PHST- 2014/02/04 00:00 [accepted]
PHST- 2014/02/19 06:00 [entrez]
PHST- 2014/02/19 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
AID - 10.3892/mmr.2014.1946 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 Apr;9(4):1460-6. doi: 10.3892/mmr.2014.1946. Epub 2014 Feb 11.