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Desflurane preconditioning protects human umbilical vein endothelial cells against anoxia/reoxygenation by upregulating NLRP12 and inhibiting non-canonical nuclear factor-κB signaling.

Abstract
Volatile anesthetics modulate endothelial cell apoptosis and inhibit nuclear factor-κB (NF-κB) signaling. In this study, we aimed to assess whether desflurane preconditioning protects human umbilical vein endothelial cells (HUVECs) agaist anoxia/reoxygenation (A/R) injury. HUVECs were pre-conditioned with desflurane (1.0 MAC) for 30 min, followed by a 15-min washout, then exposed to 60 min anoxia and 60 min reoxygenation (A/R), and incubated with 10 ng/ml tumor necrosis factor (TNF)-α for 60 min. HUVEC viability and apoptosis were measured by MTT assay and annexin V staining, and immunoblot analysis was used to measure the levels of Smac and cellular inhibitor of apoptosis 1 (cIAP1). NF-κB activation was assessed using the NF-κB signaling pathway real‑time PCR array, and the levels of NF-κB inducing kinase (NIK), p52, IκB kinase (IKK)α, p100, RelB and NLR family, pyrin domain containing 12 (NLRP12) were assessed by immunoblot analysis. Desflurane preconditioning attenuated the effects of A/R and/or A/R plus TNF-α on cell viability, decreasing the levels of Smac and enhancing the levels of of cIAP1 (P<0.05). Preconditioning with desflurane also enhanced the mRNA levels of interleukin (IL)-10 and NLRP12 in the cells exposed to A/R by 2.40- and 2.16‑fold, respectively. The HUVECs exposed to A/R had greater levels of NIK and p100 and reduced levels of p52 and IKKα. Desflurance preconditioning further increased p100 levels, decreased the level of NIK, further decreased p52 levels and further reduced IKKα levels. A/R in combination with TNF-α increased the NIK, IKKα, p100 and RelB levels, and this increase was significantly attenuated by desflurance preconditioning (all P<0.05). Desflurane preconditioning enhanced HUVEC survival and protected the cells against A/R injury, and our results suggested that this process involved the upregulation of NLRP12 and the inhibition of non-canonical NF-κB signaling.
AuthorsZhirong Sun, Jianing Lv, Yun Zhu, Dongli Song, Biao Zhu, Changhong Miao
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 36 Issue 5 Pg. 1327-34 (Nov 2015) ISSN: 1791-244X [Electronic] Greece
PMID26329693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NLRP12 protein, human
  • Tumor Necrosis Factor-alpha
  • Desflurane
  • Isoflurane
  • I-kappa B Kinase
Topics
  • Apoptosis (drug effects)
  • Cells, Cultured
  • Desflurane
  • Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
  • Humans
  • Hypoxia (drug therapy, metabolism)
  • I-kappa B Kinase (metabolism)
  • Intracellular Signaling Peptides and Proteins (metabolism)
  • Isoflurane (analogs & derivatives, pharmacology)
  • NF-kappa B (metabolism)
  • Signal Transduction (drug effects)
  • Transcriptional Activation (drug effects)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Up-Regulation (drug effects)

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