The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway.
J Neurochem
; 125(4): 620-33, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23286644
ABSTRACT
Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central-type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10⻹8 to 10⻹² M) inhibited 6-OHDA-evoked cell death in a concentration-dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo1â8 [DLeu5]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6-OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6-OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro-apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase-3 activity. Exposure of 6-OHDA-treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Neuropeptídeos
/
Proteína Quinase C
/
Cerebelo
/
Oxidopamina
/
Apoptose
/
Sistema de Sinalização das MAP Quinases
/
Inibidor da Ligação a Diazepam
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article