Antioxidant and Anti-Apoptotic Activity of Octadecaneuropeptide Against 6-OHDA Toxicity in Cultured Rat Astrocytes

• Published in: Journal of molecular neuroscience Vol. 69; no. 1; pp. 1 - 16
• Main Authors: Kaddour, Hadhemi, Hamdi, Yosra, Amri, Fatma, Bahdoudi, Seyma, Bouannee, Ibtissem, Leprince, Jérôme, Zekri, Sami, Vaudry, Hubert, Tonon, Marie-Christine, Vaudry, David, Amri, Mohamed, Mezghani, Sana, Masmoudi-Kouki, Olfa
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2019; Springer Nature B.V; Humana Press
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Apoptosis; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Caspase; Caspase 3 - metabolism; Caspase-3; Catalase; Catalase - metabolism; Cell Behavior; Cell Biology; Cell death; Cells, Cultured; Cellular Biology; Chemical Sciences; Diazepam Binding Inhibitor - pharmacology; Enzymatic activity; Gene expression; Glutathione; Glutathione peroxidase; Hydrogen peroxide; Life Sciences; Low concentrations; Medicinal Chemistry; Mitochondria; Mortality; Neurobiology; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neurology; Neurons and Cognition; Neuropeptides - pharmacology; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Octadecaneuropeptide; Oxidative stress; Oxidopamine - toxicity; Peptide Fragments - pharmacology; Peptides; Peroxidase; Pharmaceutical sciences; Pharmacology; Proteomics; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Superoxide dismutase; Superoxide Dismutase - metabolism; Time dependence; Toxicity; Transcription; Oxidative stress; Neuroprotection; 6-hydroxydopamine; Octadecaneuropeptide; Astrocytes; Cell death
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-018-1181-4

Oxidative stress, associated with various neurodegenerative diseases, promotes ROS generation, impairs cellular antioxidant defenses, and finally, triggers both neurons and astroglial cell death by apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). We have previously reported that ODN acts as a potent neuroprotective agent that prevents 6-OHDA-induced apoptotic neuronal death. The purpose of the present study was to investigate the potential glioprotective effect of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Incubation of astrocytes with graded concentrations of ODN (10 −14 to 10 −8  M) inhibited 6-OHDA-evoked cell death in a concentration- and time-dependent manner. In addition, ODN prevented the decrease of mitochondrial activity and caspase-3 activation induced by 6-OHDA. 6-OHDA-treated cells also exhibited enhanced levels of ROS associated with a generation of H 2 O 2 and O 2 °- , and a reduction of both superoxide dismutase (SOD) and catalase (CAT) activities. Co-treatment of astrocytes with low concentrations of ODN dose-dependently blocked 6-OHDA-evoked production of ROS and inhibition of antioxidant enzyme activities. Concomitantly, ODN stimulated Mn-SOD , CAT , glutathione peroxidase-1 , and sulfiredoxin-1 gene transcription and rescued 6-OHDA-associated reduced expression of endogenous antioxidant enzymes. Taken together, these data indicate that, in rat astrocytes, ODN exerts anti-apoptotic and anti-oxidative activities, and hence prevents 6-OHDA-induced oxidative assault and cell death. ODN is thus a potential candidate to delay neuronal damages in various pathological conditions involving oxidative neurodegeneration.