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

Abstract

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 μΜ. 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.

• Authors: Rui Yang, Heng-Jing Cui, Hua Wang, Yan Wang, Jian-Hua Liu, Yong Li, Yang Lu
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 124 Issue 2 Pg. 169-79 ( 2014) ISSN: 1347-8648 [Electronic] Japan
• PMID: 24463778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Inducing Factor
• BH3 Interacting Domain Death Agonist Protein
• Bid protein, rat
• Neuroprostanes
• Neurotransmitter Agents
• Reactive Oxygen Species
• Glutamic Acid
• Tyrosine
• N-stearoyltyrosine
• Lipoxygenase

Topics

• Active Transport, Cell Nucleus
• Animals
• Apoptosis Inducing Factor (metabolism)
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Cell Death (drug effects)
• Dose-Response Relationship, Drug
• Glutamic Acid (physiology, toxicity)
• Lipoxygenase (metabolism)
• Mitochondria (genetics)
• Neuroprostanes (pharmacology)
• Neurotransmitter Agents (physiology, toxicity)
• Oxidative Stress (drug effects, genetics)
• PC12 Cells
• Rats
• Reactive Oxygen Species (metabolism)
• Tyrosine (analogs & derivatives, pharmacology)
• Up-Regulation (drug effects)