Octadecaneuropeptide, ODN, Promotes Cell Survival against 6-OHDA-Induced Oxidative Stress and Apoptosis by Modulating the Expression of miR-34b, miR-29a, and miR-21in Cultured Astrocytes
Amine Bourzam,
Yosra Hamdi,
Seyma Bahdoudi,
Karthi Duraisamy,
Mouna El Mehdi,
Magali Basille-Dugay,
Omayma Dlimi,
Maher Kharrat,
Anne Vejux,
Gérard Lizard,
Taoufik Ghrairi,
Benjamin Lefranc,
David Vaudry,
Jean A. Boutin,
Jérôme Leprince,
Olfa Masmoudi-Kouki
Affiliations
Amine Bourzam
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Yosra Hamdi
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis 2092, Tunisia
Seyma Bahdoudi
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis 2092, Tunisia
Karthi Duraisamy
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Mouna El Mehdi
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Magali Basille-Dugay
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Omayma Dlimi
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Maher Kharrat
Human Genetics Laboratory (LR99ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia
Anne Vejux
Centre des Sciences du Goût et de l’Alimentation (CSGA), CNRS, INRAE, Institut Agro, Université de Bourgogne, 21000 Dijon, France
Gérard Lizard
Team Bio-PeroxIL, “Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism” (EA7270), Université de Bourgogne, Inserm, 21000 Dijon, France
Taoufik Ghrairi
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis 2092, Tunisia
Benjamin Lefranc
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
David Vaudry
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Jean A. Boutin
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Jérôme Leprince
Laboratory of Neuroendocrine, Endocrine and Germinal Differentiation and Communication (NorDiC), Inserm UMR 1239, University Rouen Normandie, 76000 Rouen, France
Olfa Masmoudi-Kouki
LR18ES03 Laboratory of Neurophysiology, Cellular Physiopathology and Valorisation of Biomolecules, Faculty of Science of Tunis, University Tunis El Manar, Tunis 2092, Tunisia
Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides including octadecaneuropeptide (ODN). We have previously reported that ODN rescues neurons and astrocytes from 6-OHDA-induced oxidative stress and cell death. The purpose of this study was to examine the potential implication of miR-34b, miR-29a, and miR-21 in the protective activity of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Flow cytometry analysis showed that 6-OHDA increased the number of early apoptotic and apoptotic dead cells while treatment with the subnanomolar dose of ODN significantly reduced the number of apoptotic cells induced by 6-OHDA. 6-OHDA-treated astrocytes exhibited the over-expression of miR-21 (+118%) associated with a knockdown of miR-34b (−61%) and miR-29a (−49%). Co-treatment of astrocytes with ODN blocked the 6-OHDA-stimulated production of ROS and NO and stimulation of Bax and caspase-3 gene transcription. Concomitantly, ODN down-regulated the expression of miR-34b and miR-29a and rescued the 6-OHDA-associated reduced expression of miR21, indicating that ODN regulates their expression during cell death. Transfection with miR-21-3p inhibitor prevented the effect of 6-OHDA against cell death. In conclusion, our study indicated that (i) the expression of miRNAs miR-34b, miR-29a, and miR-21 is modified in astrocytes under 6-OHDA injury and (ii) that ODN prevents this deregulation to induce its neuroprotective action. The present study identified miR-21 as an emerging candidate and as a promising pharmacological target that opens new neuroprotective therapeutic strategies in neurodegenerative diseases, especially in Parkinson’s disease.
