N-Stearoyltyrosine Protects Against Glutamate-Induced Oxidative Toxicity by an Apoptosis-Inducing Factor (AIF)-Mediated Caspase-Independent Cell Death Pathway

作者：Yang, Rui; Cui, Heng-Jing; Wang, Hua; Wang, Yan; Liu, Jian-Hua; Li, Yong; Lu, Yang^*

来源：Journal of Pharmacological Sciences, 2014, 124(2): 169-179.

DOI：10.1254/jphs.13184FP

• N-stearoyltyrosine
• glutamate
• oxidative toxicity
• apoptosis-inducing factor (AIF)
• caspase-independent

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 mu M. 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.

• 出版日期2014-2
• 单位上海交通大学; 河北医科大学