title: [Zileuton, a 5-lipoxygenase inhibitor, attenuates mouse microglial cell-mediated rotenone toxicity in PC12 cells].
abstract: To examine the effect of a selective inhibitor of 5-lipoxygenase (5-LOX) zileuton on microglia-mediated rotenone neurotoxicity.
  
  
  
  The supernatant from different concentrations of rotenone-stimulated mouse microglia BV2 cells was used as the conditioned media (CM) for PC12 cells. The viability of PC12 cells was determined by MTT assay and lactate dehydrogenase (LDH) release. Cell death was observed by LDH release and double fluorescence staining with Hoechst/propidiumiodide (PI). The effect of zileuton on microglia-mediated rotenone toxicity was evaluated by the above methods.
  
  
  
  Rotenone at 1-10 nmol/L was nontoxic to PC12 cells directly. However, the CM from BV2 cells that were treated with rotenone (1-10 nmol/L) resulted in toxicity of PC12 cells. The BV2 CM which stimulated with rotenone (1-10 nmol/L) induced morphological changes, reduced cell viability, and increased LDH release and cell necrosis in PC12 cells. Pretreatment of BV2 cells with the 5-LOX inhibitor zileuton (0.01-1 μmol/L) protected PC12 cells from the microglia-mediated rotenone toxicity.
  
  
  
  The 5-LOX inhibitor zileuton effectively attenuates microglia-mediated rotenone toxicity in PC12 cells. These results suggest that 5-LOX pathway may be involved in neuronal death induced by microglial inflammation.
authors.affiliation: Department of Pharmacology， Hangzhou Key Laboratory of Medical Neurobiology， School of Medicine， Hangzhou Normal University， Hangzhou 310036, China; Biotherapy Center， the General Hospital of Beijing Military Command， Beijing 100700， China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology， Hangzhou Key Laboratory of Medical Neurobiology， School of Medicine， Hangzhou Normal University， Hangzhou 310036, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology， Zhejiang University School of Medicine， Hangzhou 310058, China.
authors.forename: Dong-min
authors.initials: DM
authors.lastname: Xu
authors.affiliation: Department of Pharmacology， Zhejiang University School of Medicine， Hangzhou 310058, China.
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Wang
authors.affiliation: Department of Pharmacology， Hangzhou Key Laboratory of Medical Neurobiology， School of Medicine， Hangzhou Normal University， Hangzhou 310036, China.
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Wang
authors.affiliation: DDepartment of Pharmacology， Hangzhou Key Laboratory of Medical Neurobiology， School of Medicine， Hangzhou Normal University， Hangzhou 310036, China.
authors.forename: Cheng-tan
authors.initials: CT
authors.lastname: Li
authors.affiliation: Department of Pharmacology， Zhejiang University School of Medicine， Hangzhou 310058, China.
authors.forename: Er-qing
authors.initials: EQ
authors.lastname: Wei
authors.affiliation: Department of Pharmacology， Hangzhou Key Laboratory of Medical Neurobiology， School of Medicine， Hangzhou Normal University， Hangzhou 310036, China.
authors.forename: Li-hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology*; D016716:PC12 Cells; D051381:Rats; D012402:Rotenone / Q000633:toxicity*
chemical_list: D016859:Lipoxygenase Inhibitors; D012402:Rotenone; C063449:zileuton; D006918:Hydroxyurea