Cargando…
Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells
The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidati...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287847/ https://www.ncbi.nlm.nih.gov/pubmed/32414101 http://dx.doi.org/10.3390/molecules25102296 |
_version_ | 1783545144310497280 |
---|---|
author | Yammine, Aline Nury, Thomas Vejux, Anne Latruffe, Norbert Vervandier-Fasseur, Dominique Samadi, Mohammad Greige-Gerges, Hélène Auezova, Lizette Lizard, Gérard |
author_facet | Yammine, Aline Nury, Thomas Vejux, Anne Latruffe, Norbert Vervandier-Fasseur, Dominique Samadi, Mohammad Greige-Gerges, Hélène Auezova, Lizette Lizard, Gérard |
author_sort | Yammine, Aline |
collection | PubMed |
description | The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage. As there are numerous data in favor of the prevention of neurodegeneration by the Mediterranean diet, this study aimed to evaluate the potential of a series of polyphenols (resveratrol, RSV; quercetin, QCT; and apigenin, API) as well as ω3 and ω9 unsaturated fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA, and oleic acid, OA) widely present in this diet, to prevent 7KC (50 µM)-induced dysfunction of N2a neuronal cells. When polyphenols and fatty acids were used at non-toxic concentrations (polyphenols: ≤6.25 µM; fatty acids: ≤25 µM) as defined by the fluorescein diacetate assay, they greatly reduce 7KC-induced toxicity. The cytoprotective effects observed with polyphenols and fatty acids were comparable to those of α-tocopherol (400 µM) used as a reference. These polyphenols and fatty acids attenuate the overproduction of reactive oxygen species and the 7KC-induced drop in mitochondrial transmembrane potential (ΔΨm) measured by flow cytometry after dihydroethidium and DiOC(6)(3) staining, respectively. Moreover, the studied polyphenols and fatty acids reduced plasma membrane permeability considered as a criterion for cell death measured by flow cytometry after propidium iodide staining. Our data show that polyphenols (RSV, QCT and API) as well as ω3 and ω9 unsaturated fatty acids (ALA, EPA, DHA and OA) are potent cytoprotective agents against 7KC-induced neurotoxicity in N2a cells. Their cytoprotective effects could partly explain the benefits of the Mediterranean diet on human health, particularly in the prevention of neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-7287847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72878472020-06-15 Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells Yammine, Aline Nury, Thomas Vejux, Anne Latruffe, Norbert Vervandier-Fasseur, Dominique Samadi, Mohammad Greige-Gerges, Hélène Auezova, Lizette Lizard, Gérard Molecules Article The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage. As there are numerous data in favor of the prevention of neurodegeneration by the Mediterranean diet, this study aimed to evaluate the potential of a series of polyphenols (resveratrol, RSV; quercetin, QCT; and apigenin, API) as well as ω3 and ω9 unsaturated fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA, and oleic acid, OA) widely present in this diet, to prevent 7KC (50 µM)-induced dysfunction of N2a neuronal cells. When polyphenols and fatty acids were used at non-toxic concentrations (polyphenols: ≤6.25 µM; fatty acids: ≤25 µM) as defined by the fluorescein diacetate assay, they greatly reduce 7KC-induced toxicity. The cytoprotective effects observed with polyphenols and fatty acids were comparable to those of α-tocopherol (400 µM) used as a reference. These polyphenols and fatty acids attenuate the overproduction of reactive oxygen species and the 7KC-induced drop in mitochondrial transmembrane potential (ΔΨm) measured by flow cytometry after dihydroethidium and DiOC(6)(3) staining, respectively. Moreover, the studied polyphenols and fatty acids reduced plasma membrane permeability considered as a criterion for cell death measured by flow cytometry after propidium iodide staining. Our data show that polyphenols (RSV, QCT and API) as well as ω3 and ω9 unsaturated fatty acids (ALA, EPA, DHA and OA) are potent cytoprotective agents against 7KC-induced neurotoxicity in N2a cells. Their cytoprotective effects could partly explain the benefits of the Mediterranean diet on human health, particularly in the prevention of neurodegenerative diseases. MDPI 2020-05-13 /pmc/articles/PMC7287847/ /pubmed/32414101 http://dx.doi.org/10.3390/molecules25102296 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yammine, Aline Nury, Thomas Vejux, Anne Latruffe, Norbert Vervandier-Fasseur, Dominique Samadi, Mohammad Greige-Gerges, Hélène Auezova, Lizette Lizard, Gérard Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title | Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title_full | Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title_fullStr | Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title_full_unstemmed | Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title_short | Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells |
title_sort | prevention of 7-ketocholesterol-induced overproduction of reactive oxygen species, mitochondrial dysfunction and cell death with major nutrients (polyphenols, ω3 and ω9 unsaturated fatty acids) of the mediterranean diet on n2a neuronal cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287847/ https://www.ncbi.nlm.nih.gov/pubmed/32414101 http://dx.doi.org/10.3390/molecules25102296 |
work_keys_str_mv | AT yamminealine preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT nurythomas preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT vejuxanne preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT latruffenorbert preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT vervandierfasseurdominique preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT samadimohammad preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT greigegergeshelene preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT auezovalizette preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells AT lizardgerard preventionof7ketocholesterolinducedoverproductionofreactiveoxygenspeciesmitochondrialdysfunctionandcelldeathwithmajornutrientspolyphenolsō3andō9unsaturatedfattyacidsofthemediterraneandietonn2aneuronalcells |