Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue
On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, −3 and −7 cleavage, PARP degradation) and...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000069 |
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| author | Aline Yammine Imen Ghzaiel Vivien Pires Amira Zarrouk Omar Kharoubi Hélène Greige-Gerges Lizette Auezova Gérard Lizard Anne Vejux |
| author_facet | Aline Yammine Imen Ghzaiel Vivien Pires Amira Zarrouk Omar Kharoubi Hélène Greige-Gerges Lizette Auezova Gérard Lizard Anne Vejux |
| author_sort | Aline Yammine |
| collection | DOAJ |
| description | On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, −3 and −7 cleavage, PARP degradation) and autophagy (increased ratio LC3-II / LC3-I). Oxidative stress was strongly attenuated by diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial and peroxisomal morphological and functional changes were also observed. Down regulation of PDK1 / Akt signaling pathways as well as of GSK3 / Mcl-1 and Nrf2 pathways were simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events were prevented by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by LY-294002, a PI3-K inhibitor, demonstrated an essential role of PI3-K in cell rescue. The rupture of oxidative stress in 7-ketocholesterol-induced oxiapoptophagy was also associated with important modifications of glutathione peroxidase, superoxide dismutase and catalase activities as well as of glutathione peroxidase-1, superoxide dismutase-1 and catalase level and expression. These events were also counteracted by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by mercaptosuccinic acid, a glutathione peroxidase inhibitor, showed an essential role of this enzyme in cell rescue. Altogether, our data support that the reactivation of PI3-K and glutathione peroxidase activities by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol are essential to prevent 7KC-induced oxiapoptophagy. |
| first_indexed | 2024-03-08T00:22:35Z |
| format | Article |
| id | doaj.art-16ff6ffe11fd4d219d22fc7ddaa205b3 |
| institution | Directory Open Access Journal |
| issn | 2666-027X |
| language | English |
| last_indexed | 2025-03-21T17:42:18Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj.art-16ff6ffe11fd4d219d22fc7ddaa205b32024-06-12T04:47:20ZengElsevierCurrent Research in Toxicology2666-027X2024-01-016100153Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescueAline Yammine0Imen Ghzaiel1Vivien Pires2Amira Zarrouk3Omar Kharoubi4Hélène Greige-Gerges5Lizette Auezova6Gérard Lizard7Anne Vejux8Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France; Bioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Fanar, Jdeidet P.O. Box 90656, LebanonTeam 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France; Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Faculty of Medicine, University of Monastir, LR12ES05, Monastir 5000, Tunisia; Université Clermont Auvergne, Clermont Auvergne INP, CNRS, Institut Pascal, F-63000 Clermont-Ferrand, FranceTeam 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France; Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000 Dijon, FranceLab-NAFS 'Nutrition-Functional Food & Vascular Health', Faculty of Medicine, University of Monastir, LR12ES05, Monastir 5000, Tunisia; Faculty of Medicine, University of Sousse, Sousse 4000, TunisiaUniversity Oran 1 ABB: Laboratory of Experimental Biotoxicology, Biodepollution and Phytoremediation, Faculty of Life and Natural Sciences, Oran, AlgeriaBioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Fanar, Jdeidet P.O. Box 90656, LebanonBioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Fanar, Jdeidet P.O. Box 90656, LebanonTeam 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France; Corresponding authors.Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France; Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000 Dijon, France; Corresponding authors.On murine N2a cells, 7-ketocholesterol induced an oxiapotophagic mode of cell death characterized by oxidative stress (reactive oxygen species overproduction on whole cells and at the mitochondrial level; lipid peroxidation), apoptosis induction (caspase-9, −3 and −7 cleavage, PARP degradation) and autophagy (increased ratio LC3-II / LC3-I). Oxidative stress was strongly attenuated by diphenyleneiodonium chloride which inhibits NAD(P)H oxidase. Mitochondrial and peroxisomal morphological and functional changes were also observed. Down regulation of PDK1 / Akt signaling pathways as well as of GSK3 / Mcl-1 and Nrf2 pathways were simultaneously observed in 7-ketocholesterol-induced oxiapoptophagy. These events were prevented by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by LY-294002, a PI3-K inhibitor, demonstrated an essential role of PI3-K in cell rescue. The rupture of oxidative stress in 7-ketocholesterol-induced oxiapoptophagy was also associated with important modifications of glutathione peroxidase, superoxide dismutase and catalase activities as well as of glutathione peroxidase-1, superoxide dismutase-1 and catalase level and expression. These events were also counteracted by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol. The inhibition of the cytoprotection by mercaptosuccinic acid, a glutathione peroxidase inhibitor, showed an essential role of this enzyme in cell rescue. Altogether, our data support that the reactivation of PI3-K and glutathione peroxidase activities by α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol are essential to prevent 7KC-induced oxiapoptophagy.http://www.sciencedirect.com/science/article/pii/S2666027X240000697-ketocholesterolα-tocopherolEicosapentaenoic acidα-linolenic acidOleic acidglutathione peroxidase |
| spellingShingle | Aline Yammine Imen Ghzaiel Vivien Pires Amira Zarrouk Omar Kharoubi Hélène Greige-Gerges Lizette Auezova Gérard Lizard Anne Vejux Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue Current Research in Toxicology 7-ketocholesterol α-tocopherol Eicosapentaenoic acid α-linolenic acid Oleic acid glutathione peroxidase |
| title | Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue |
| title_full | Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue |
| title_fullStr | Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue |
| title_full_unstemmed | Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue |
| title_short | Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol – Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue |
| title_sort | cytoprotective effects of α linolenic acid eicosapentaenoic acid docosahexaenoic acid oleic acid and α tocopherol on 7 ketocholesterol induced oxiapoptophagy major roles of pi3 k pdk 1 akt signaling pathway and glutathione peroxidase activity in cell rescue |
| topic | 7-ketocholesterol α-tocopherol Eicosapentaenoic acid α-linolenic acid Oleic acid glutathione peroxidase |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000069 |
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