title: 2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells.
abstract: BACKGROUND
  β-Amyloid protein (Aβ) accumulation and caspase activation have been shown to contribute to Alzheimer disease neuropathogenesis. Aβ is produced from amyloid precursor protein through proteolytic processing by aspartyl protease β-site amyloid precursor protein-cleaving enzyme (BACE). The inhaled anesthetic isoflurane has been shown to induce caspase activation and increase levels of BACE and Aβ. However, the underlying mechanisms and interventions of the isoflurane-induced neurotoxicity remain largely to be determined. The glucose analog 2-deoxy-d-glucose (2-DG) has neuroprotective effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3 activation and the increase in the levels of BACE and reactive oxygen species (ROS) induced by isoflurane.
  
  
  METHODS
  H4 human neuroglioma cells were treated with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2% isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE, cytosolic calcium, and ROS were determined. Two-way analysis of variance was used to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and levels of BACE and ROS.
  
  
  RESULTS
  In H4 human neuroglioma cells, 2-DG reduced the caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P = 0.014).
  
  
  CONCLUSIONS
  These results suggest that 2-DG may decrease oxidative stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced neurotoxicity.
authors.affiliation: Geriatric Anesthesia Research Unit, Massachusetts General Hospital and Harvard Medical School, 149 13th St., Room 4310, Charlestown, MA 02129-2060, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chuxiong
authors.initials: C
authors.lastname: Pan
authors.forename: Sayre
authors.initials: S
authors.lastname: McAuliffe
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
authors.forename: Yun
authors.initials: Y
authors.lastname: Yue
authors.forename: Weimin
authors.initials: W
authors.lastname: Liang
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
mesh_terms: D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D003603:Cytotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D003847:Deoxyglucose / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007530:Isoflurane / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D003603:Cytotoxins; D017382:Reactive Oxygen Species; D003847:Deoxyglucose; D007530:Isoflurane