N-stearoyltyrosine protects against glutamate-induced oxidative toxicity by an apoptosis-inducing factor (AIF)-mediated caspase-independent cell death pathway.
J Pharmacol Sci
; 124(2): 169-79, 2014.
Article
em En
| MEDLINE
| ID: mdl-24463778
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tirosina
/
Estresse Oxidativo
/
Neurotransmissores
/
Ácido Glutâmico
/
Fator de Indução de Apoptose
/
Neuroprostanos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Ano de publicação:
2014
Tipo de documento:
Article