N-stearoyltyrosine protects against glutamate-induced oxidative toxicity by an apoptosis-inducing factor (AIF)-mediated caspase-independent cell death pathway

N-stearoyltyrosine (nstyr),a synthesized anandamide (aea) analogue,could exert potent neuroprotective effects on cerebral ischemia models both in vivo and in vitro via intervening in multiple injuries. glutamate,a major excitatory neurotransmitter,plays a critical role during stroke/cerebral ischemia. in this study,we explored the protective effects of nstyr on glutamate neurotoxicity in pc12 cells and investigated its underlying mechanisms. nstyr treatment attenuated glutamate-induced oxidative toxicity in a dose-dependent manner and the best performance was observed at 10 μm. nstyr treatment suppressed glutamate-induced upregulation of lipoxygenase 12/15 (lox 12/15) activity and reactive oxygen species (ros) elevation,attenuated the increase of bh3-interacting domain death agonist (bid) in the mitochondria,prevented the loss of mitochondria membrane potential and consequently inhibited apoptosis-inducing factor (aif) translocation into the nucleus. the results demonstrated that nstyr could protect cells against aif-mediated caspase-independent cell death induced by glutamate,which may be due to the blockage of bid-mediated mitochondrial damage via reducing lox 12/15 activity and ros accumulation. © 2014 the japanese pharmacological society.