Skip to Main content Skip to Navigation
Journal articles

The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway

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 (10⁻¹⁸ to 10⁻¹² 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, cyclo₁₋₈ [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.
Complete list of metadatas

https://hal-normandie-univ.archives-ouvertes.fr/hal-01962763
Contributor : Jérôme Leprince <>
Submitted on : Thursday, December 20, 2018 - 6:31:08 PM
Last modification on : Wednesday, September 23, 2020 - 4:33:49 AM

Links full text

Identifiers

Citation

Hadhemi Kaddour, Yosra Hamdi, David Vaudry, Magalie Basille, Laurence Desrues, et al.. The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway. Journal of Neurochemistry, Wiley, 2013, 125 (4), pp.620-633. ⟨10.1111/jnc.12140⟩. ⟨hal-01962763⟩

Share

Metrics

Record views

52