Abstract | BACKGROUND:
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.
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Authors | Juan Yi, Yijun Zheng, Changhong Miao, Jianguo Tang, Biao Zhu |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 6
Pg. e66576
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23799118
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3-(4-methylphenylsulfonyl)-2-propenenitrile
- Anesthetics, Inhalation
- NF-kappa B
- Nitriles
- Sulfones
- Desflurane
- Isoflurane
- Superoxide Dismutase
- Caspase 3
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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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