Abstract
AIM: 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). CONCLUSION: 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.