5-S-GAD attenuates Fe²+-induced lipid peroxidation and cell death in a neuronal cell model

Iron accumulation in brain is associated with a number of common neurodegenerative disorders. N-β-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel catechol derivative, was isolated from adult flesh fly as a defense substance. We examined the effect of 5-S-GAD on Fe²+-induced lipid peroxidation and cell death in PC12 cells. Treatment of PC12 cells with Fe²+ (1-20 μM) for 24 h induced lipid peroxidation and cell death in a dose-dependent manner. Butylated hydroxyanisole and α-tocopherol inhibited Fe²+-induced lipid peroxidation and cell death. 5-S-GAD inhibited Fe²+-induced lipid peroxidation and cell death. 5-S-GAD protected PC12 cells from Fe²+-induced cell death possibly by blocking lipid peroxidation.