title: Rosiglitazone protects neuroblastoma cells against advanced glycation end products-induced injury.
abstract: OBJECTIVE
  To investigate the protective effects of rosiglitazone (RGZ) against the neuronal toxicity induced by advanced glycation end products (AGEs) and the underlying mechanisms.
  
  
  METHODS
  Neuroblastoma cell line SH-SY5Y was used. Cell viability and apoptosis were assessed using MTT assay and flow cytometry, respectively. Superoxide dismutase (SOD) and catalase activities were measured using biochemical methods. Intracellular reactive oxygen species (ROS) were monitored using 2',7'-dichlorodihydro-fluorescein diacetate (DCFH-DA). Secreted β-amyloid(1-42) (Aβ(1-42)) level was assessed by ELISA. The expression of mRNA of Bcl2, Bax, Caspase3, Aβ precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1), and insulin degrading enzyme (IDE) were measured using quantitative real-time PCR (Q-PCR), and their protein levels were examined using Western blot.
  
  
  RESULTS
  RGZ (0.1-10 μmol/L) significantly increased the cell viability that was reduced by AGEs (1000 μg/mL). RGZ (10 μmol/L) significantly ameliorated AGEs-triggered downregulation of SOD and catalase, and production of ROS. It also reversed Bcl2 downregulation, Bax upregulation and Caspase3 expression caused by AGEs. Moreover, it significantly attenuated AGEs-induced Aβ secretion and APP protein upregulation. RGZ did not affect BACE1 expression, but induced IDE expression, which promoted degradation of Aβ. All the effects were blocked by the specific PPARγ antagonist GW9662 (10 μmol/L).
  
  
  CONCLUSIONS
  RGZ protects the euroblastoma cells against AGEs-induced injury via its anti-oxidative, anti-apoptotic and anti-inflammatory properties that seems to be mediated by PPARγ activation. The results suggest a beneficial role for RGZ in the treatment of Alzheimer's disease.
authors.affiliation: Department of Geriatrics, the Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Chun-jiang
authors.initials: CJ
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lu-yang
authors.initials: LY
authors.lastname: Cheng
authors.forename: Yi-na
authors.initials: YN
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D017127:Glycation End Products, Advanced; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone