Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.
Identifieur interne : 000264 ( Main/Exploration ); précédent : 000263; suivant : 000265Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.
Auteurs : Imène Achour [Canada] ; Anne-Marie Arel-Dubeau [Canada] ; Justine Renaud [Canada] ; Manon Legrand [Canada] ; Everaldo Attard [Malte] ; Marc Germain [Canada] ; Maria-Grazia Martinoli [Canada]Source :
- International journal of molecular sciences [ 1422-0067 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Autophagy (drug effects), Cell Death (drug effects), Iridoids (pharmacology), Mitochondria (drug effects), Mitochondria (metabolism), Nerve Degeneration (metabolism), Oxidative Stress (drug effects), Oxidopamine (pharmacology), PC12 Cells, Parkinson Disease (metabolism), Rats, Reactive Oxygen Species (metabolism), Superoxides (metabolism).
- MESH :
- chemical , metabolism : Reactive Oxygen Species, Superoxides.
- chemical , pharmacology : Iridoids, Oxidopamine.
- drug effects : Autophagy, Cell Death, Mitochondria, Oxidative Stress.
- metabolism : Mitochondria, Nerve Degeneration, Parkinson Disease.
- Animals, PC12 Cells, Rats.
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.
DOI: 10.3390/ijms17081293
PubMed: 27517912
Affiliations:
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Manon.legrand@uqtr.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7</wicri:regionArea><wicri:noRegion>QC G9A 5H7</wicri:noRegion></affiliation></author><author><name sortKey="Attard, Everaldo" sort="Attard, Everaldo" uniqKey="Attard E" first="Everaldo" last="Attard">Everaldo Attard</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Earth Systems, University of Malta, Msida MSD 2080, Malta. everaldo.attard@um.edu.mt.</nlm:affiliation><country xml:lang="fr">Malte</country><wicri:regionArea>Institute of Earth Systems, University of Malta, Msida MSD 2080</wicri:regionArea><wicri:noRegion>Msida MSD 2080</wicri:noRegion></affiliation></author><author><name sortKey="Germain, Marc" sort="Germain, Marc" uniqKey="Germain M" first="Marc" last="Germain">Marc Germain</name><affiliation wicri:level="1"><nlm:affiliation>Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. Marc.Germain1@uqtr.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7</wicri:regionArea><wicri:noRegion>QC G9A 5H7</wicri:noRegion></affiliation></author><author><name sortKey="Martinoli, Maria Grazia" sort="Martinoli, Maria Grazia" uniqKey="Martinoli M" first="Maria-Grazia" last="Martinoli">Maria-Grazia Martinoli</name><affiliation wicri:level="1"><nlm:affiliation>Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. maria-grazia.martinoli@uqtr.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Cellular Traffic Research Group, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7</wicri:regionArea><wicri:noRegion>QC G9A 5H7</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Autophagy (drug effects)</term><term>Cell Death (drug effects)</term><term>Iridoids (pharmacology)</term><term>Mitochondria (drug effects)</term><term>Mitochondria (metabolism)</term><term>Nerve Degeneration (metabolism)</term><term>Oxidative Stress (drug effects)</term><term>Oxidopamine (pharmacology)</term><term>PC12 Cells</term><term>Parkinson Disease (metabolism)</term><term>Rats</term><term>Reactive Oxygen Species (metabolism)</term><term>Superoxides (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Reactive Oxygen Species</term><term>Superoxides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Iridoids</term><term>Oxidopamine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Cell Death</term><term>Mitochondria</term><term>Oxidative Stress</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mitochondria</term><term>Nerve Degeneration</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>PC12 Cells</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Malte</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Achour, Imene" sort="Achour, Imene" uniqKey="Achour I" first="Imène" last="Achour">Imène Achour</name></noRegion><name sortKey="Arel Dubeau, Anne Marie" sort="Arel Dubeau, Anne Marie" uniqKey="Arel Dubeau A" first="Anne-Marie" last="Arel-Dubeau">Anne-Marie Arel-Dubeau</name><name sortKey="Germain, Marc" sort="Germain, Marc" uniqKey="Germain M" first="Marc" last="Germain">Marc Germain</name><name sortKey="Legrand, Manon" sort="Legrand, Manon" uniqKey="Legrand M" first="Manon" last="Legrand">Manon Legrand</name><name sortKey="Martinoli, Maria Grazia" sort="Martinoli, Maria Grazia" uniqKey="Martinoli M" first="Maria-Grazia" last="Martinoli">Maria-Grazia Martinoli</name><name sortKey="Renaud, Justine" sort="Renaud, Justine" uniqKey="Renaud J" first="Justine" last="Renaud">Justine Renaud</name></country><country name="Malte"><noRegion><name sortKey="Attard, Everaldo" sort="Attard, Everaldo" uniqKey="Attard E" first="Everaldo" last="Attard">Everaldo Attard</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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