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Desflurane preconditioning induces oscillation of NF-κB in human umbilical vein endothelial cells.

AbstractBACKGROUND:
Nuclear factor kappa B (NF-κB) has been implicated in anesthetic preconditioning (APC) induced protection against anoxia and reoxygenation (A/R) injury. The authors hypothesized that desflurane preconditioning would induce NF-κB oscillation and prevent endothelial cells apoptosis.
METHODS:
A human umbilical vein endothelial cells (HUVECs) A/R injury model was used. A 30 minute desflurane treatment was initiated before anoxia. NF-κB inhibitor BAY11-7082 was administered in some experiments before desflurane preconditioning. Cells apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate staining and cell viability was evaluated by modified tertrozalium salt (MTT) assay. The cellular superoxide dismutases (SOD) activitiy were tested by water-soluble tetrazolium salt (WST-1) assay. NF-κB p65 subunit nuclear translocation was detected by immunofluorescence staining. Expression of inhibitor of NF-κB-α (IκBα), NF-κB p65 and cellular inhibitor of apoptosis 1 (c-IAP1), B-cell leukemia/lymphoma 2 (Bcl-2), cysteine containing aspartate specific protease 3 (caspases-3) and second mitochondrial-derived activator of caspase (SMAC/DIABLO) were determined by western blot.
RESULTS:
Desflurane preconditioning caused phosphorylation and nuclear translocation of NF-κB before anoxia, on the contrary, induced the synthesis of IκBα and inhibition of NF-κB after reoxygenation. Desflurane preconditioning up-regulated the expression of c-IAP1 and Bcl-2, blocked the cleavage of caspase-3 and reduced SMAC release, and decreased the cell death of HUVECs after A/R. The protective effect was abolished by BAY11-7082 administered before desflurane.
CONCLUSIONS:
The results demonstrated that desflurane activated NF-κB during the preconditioning period and inhibited excessive activation of NF-κB in reperfusion. And the oscillation of NF-κB induced by desflurane preconditioning finally up-regulated antiapoptotic proteins expression and protected endothelial cells against A/R.
AuthorsJuan Yi, Yijun Zheng, Changhong Miao, Jianguo Tang, Biao Zhu
JournalPloS one (PLoS One) Vol. 8 Issue 6 Pg. e66576 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23799118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Anesthetics, Inhalation
  • NF-kappa B
  • Nitriles
  • Sulfones
  • Desflurane
  • Isoflurane
  • Superoxide Dismutase
  • Caspase 3
Topics
  • Anesthetics, Inhalation (pharmacology)
  • Apoptosis
  • Caspase 3 (metabolism)
  • Cells, Cultured
  • Desflurane
  • Endothelium, Vascular (cytology, drug effects, enzymology, metabolism)
  • Flow Cytometry
  • Humans
  • Isoflurane (analogs & derivatives, pharmacology)
  • NF-kappa B (antagonists & inhibitors, metabolism)
  • Nitriles (pharmacology)
  • Proteolysis
  • Sulfones (pharmacology)
  • Superoxide Dismutase (metabolism)
  • Umbilical Veins (cytology, drug effects, enzymology, metabolism)

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