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

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Abstract

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 H2O2 and O2°-, 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.

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Abbreviations

6-OHDA:

6-hydroxydopamine

CNS:

Central nervous system

DBI:

Diazepam-binding inhibitor

DCFH:

2′,7′-dichlorodihydrofluorescein

JC-1:

5,5″,6,6″-tetrachloro-1,1″,3,3″-tetraethylbenzimidazolylcarbocyanine iodide

DHE:

Dihydroethidium

DHR123:

Dihydrorhodamine 123

FDA:

Fluorescein diacetate

Gpx:

Glutathione peroxidase

H2O2 :

Hydrogen peroxide

LDH:

Lactate dehydrogenase

NBT:

Nitrotetrazolium blue chloride

O2° :

Superoxide anions

ODN:

Octadecaneuropeptide

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

Srxn:

Sulfiredoxin

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Acknowledgments

This work was supported by the France-Tunisia CMCU-Campus France/PHC Utique 16G0820/34940PK exchange program (to Olfa Masmoudi-Kouki and David Vaudry), Alternance scholarship of Tunisian Higher Education Ministry and the Laboratory of Neurophysiology, Cellular Physiopathology and Biomolecules Valorisation. LR18ES03, INSERM (U1239), the European Regional Development Fund (PACT-CBS and PHEDERCPG projects), and the Region Normandy. Europe gets involved in Normandy with European Regional Development Fund (ERDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Olfa Masmoudi-Kouki.

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Kaddour, H., Hamdi, Y., Amri, F. et al. Antioxidant and Anti-Apoptotic Activity of Octadecaneuropeptide Against 6-OHDA Toxicity in Cultured Rat Astrocytes. J Mol Neurosci 69, 1–16 (2019). https://doi.org/10.1007/s12031-018-1181-4

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  • DOI: https://doi.org/10.1007/s12031-018-1181-4

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