title: Dexmedetomidine protects against oxygen-glucose deprivation-induced injury through the I2 imidazoline receptor-PI3K/AKT pathway in rat C6 glioma cells.
abstract: OBJECTIVE
  To explore the protection and the mechanism of dexmedetomidine on the oxygen-glucose deprivation (OGD) insults in rat C6 glioma cells.
  
  
  METHODS
  Cells were subjected to OGD then assessed by viability studies. After dexmedetomidine treatment, p-AKT, hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF) and RTP801 expression were measured.
  
  
  RESULTS
  Three hours of OGD decreased cell viability to 48.8%, which was reversed to 67.4% by 1 µm dexmedetomidine. Hoechst 33342 and propidium iodide double stains showed that the protection of dexmedetomidine was mainly by an anti-apoptosis effect, which was also strengthened by decreasing caspase-3 expression. Dexmedetomidine protection was mainly blocked by the I2 imidazoline receptor antagonist idazoxan and BU 224, but not by the α(1)-adrenoceptor antagonist prazosin, the α(2)-adrenoceptor antagonist yohimbine and RX 821002, or the I1 imidazoline receptor antagonist efaroxan. On the other hand, dexmedetomidine enhanced AKT phosphorylation. Furthermore, the protection of dexmedetomidine was blocked by the PI3K/AKT inhibitor wortmannin. The proteins of HIF-1α, VEGF and RTP801 were significantly increased by dexmedetomidine treatment.
  
  
  CONCLUSIONS
  Dexmedetomidine activated the I2 imidazoline receptor-PI3K/AKT pathway, and up-regulated HIF-1α, VEGF and RTP801 expression to protect against OGD-induced injury in rat C6 cells.
authors.affiliation: Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Fengjiang
authors.initials: F
authors.lastname: Zhang
authors.forename: Tingting
authors.initials: T
authors.lastname: Ding
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Zhong
authors.forename: Haibin
authors.initials: H
authors.lastname: Dai
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020927:Dexmedetomidine; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019329:Idazoxan; D007093:Imidazoles; D054755:Imidazoline Receptors; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C105826:BU 224; C000632146:Ddit4 protein, rat; C487767:imidazoline receptor 2