PMID- 18420862
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20181201
IS  - 1526-7598 (Electronic)
IS  - 0003-2999 (Linking)
VI  - 106
IP  - 5
DP  - 2008 May
TI  - Desflurane preconditioning inhibits endothelial nuclear factor-kappa-B activation 
      by targeting the proximal end of tumor necrosis factor-alpha signaling.
PG  - 1473-9, table of contents
LID - 10.1213/ane.0b013e318168b3f2 [doi]
AB  - BACKGROUND: Volatile anesthetics interfere with inflammatory cytokine production 
      and expression of adhesion molecules which are critical for ischemia reperfusion 
      induced injury. Nuclear factor (NF)-kappaB has been reported to be suppressed in 
      this process, but the detailed molecular mechanism is still unclear. METHODS: In 
      this study, ECV304 (a human umbilical vein endothelial cell line) was 
      preconditioned with 30 min desflurane (1 minimal alveolar concentration), after 
      15 min washout, 30 min anoxia, and 60 min reoxygenation was performed. ECV304 was 
      finally stimulated with tumor necrosis factor (TNF)-alpha (10 ng/mL). Control 
      groups, which were not preconditioned and/or not stimulated, were also included 
      in the protocol. IkappaB-alpha, phospho-IkappaB-alpha, phospho-IkappaB kinase 
      (IKKalpha)/IKKbeta, and phospho-p38 were detected by Western blotting. The 
      nuclear NF-kappaB p65 subunit was measured by subcellular fractionation and 
      Western blotting. The surface expression of TNF-R1 was measured by flow 
      cytometry. Receptor-associated signaling adaptors, e.g., TNF receptor-associated 
      factor 2 (TRAF2) and IKK-alpha, were evaluated by immunoprecipitation by TNF-R1 
      antibody and subsequent Western blotting. RESULTS: Desflurane preconditioning 
      inhibits IkappaB-alpha phosphorylation, degradation, and p65 nuclear 
      localization. Desflurane also affects p38 phosphorylation, which is needed for 
      optimal inflammatory response. The phosphorylation of IKKalpha/IKKbeta was 
      suppressed by preconditioning while the surface abundance of TNF-R1 was not 
      affected. The association of TRAF2 and IKK-alpha with TNF-R1 was compromised by 
      desflurane. CONCLUSIONS: Our results suggest that the molecular target of 
      desflurane in the NF-kappaB pathway is upstream of IKK activation. The abundance 
      of TNF-R1 on the cell membrane is not affected by anesthetic preconditioning. We 
      suggest that desflurane preconditioning targets the proximal end of TNF-alpha 
      signaling.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of Anesthesiology, Zhongshan Hospital, Fudan University, Fenglin Road 
      180, Shanghai 200032, China.
FAU - Zhang, Xiaonan
AU  - Zhang X
FAU - Zhu, Biao
AU  - Zhu B
FAU - Xue, Zhanggang
AU  - Xue Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesth Analg
JT  - Anesthesia and analgesia
JID - 1310650
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - CRS35BZ94Q (Desflurane)
RN  - CYS9AKD70P (Isoflurane)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Cell Line
MH  - Desflurane
MH  - Endothelial Cells/*drug effects/enzymology/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - I-kappa B Proteins/metabolism
MH  - Isoflurane/*analogs & derivatives/pharmacology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Phosphorylation
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Reperfusion Injury/*metabolism/prevention & control
MH  - Signal Transduction/*drug effects
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2008/04/19 09:00
MHDA- 2008/05/02 09:00
CRDT- 2008/04/19 09:00
PHST- 2008/04/19 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2008/04/19 09:00 [entrez]
AID - 106/5/1473 [pii]
AID - 10.1213/ane.0b013e318168b3f2 [doi]
PST - ppublish
SO  - Anesth Analg. 2008 May;106(5):1473-9, table of contents. doi: 
      10.1213/ane.0b013e318168b3f2.