Desflurane Preconditioning Induces Oscillation of NF-kappa B in Human Umbilical Vein Endothelial Cells

作者：Yi Juan; Zheng Yijun; Miao Changhong; Tang Jianguo; Zhu Biao^*

来源：PLos One, 2013, 8(6): e66576.

DOI：10.1371/journal.pone.0066576

Background: Nuclear factor kappa B (NF-kappa B) 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 kappa B 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-kappa B 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-kappa B p65 subunit nuclear translocation was detected by immunofluorescence staining. Expression of inhibitor of NF-kappa B-alpha (IkB alpha), NF-kappa B 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-kappa B before anoxia, on the contrary, induced the synthesis of I kappa B alpha and inhibition of NF-kappa B after reoxygenation. Desflurane preconditioning upregulated 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-kappa B during the preconditioning period and inhibited excessive activation of NF-kappa B in reperfusion. And the oscillation of NF-kappa B induced by desflurane preconditioning finally upregulated antiapoptotic proteins expression and protected endothelial cells against A/R.

• 出版日期2013-6-17
• 单位复旦大学