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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.
Yammine, Aline; Ghzaiel, Imen; Pires, Vivien; Zarrouk, Amira; Kharoubi, Omar; Greige-Gerges, Hélène; Auezova, Lizette; Lizard, Gérard; Vejux, Anne.
Afiliação
  • Yammine A; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France.
  • Ghzaiel I; Bioactive Molecules Research Laboratory, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Fanar, Jdeidet P.O. Box 90656, Lebanon.
  • Pires V; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France.
  • Zarrouk A; Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Faculty of Medicine, University of Monastir, LR12ES05, Monastir 5000, Tunisia.
  • Kharoubi O; Université Clermont Auvergne, Clermont Auvergne INP, CNRS, Institut Pascal, F-63000 Clermont-Ferrand, France.
  • Greige-Gerges H; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA7270 / Inserm, University of Bourgogne, 21000 Dijon, France.
  • Auezova L; Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, F-21000 Dijon, France.
  • Lizard G; Lab-NAFS 'Nutrition-Functional Food & Vascular Health', Faculty of Medicine, University of Monastir, LR12ES05, Monastir 5000, Tunisia.
  • Vejux A; Faculty of Medicine, University of Sousse, Sousse 4000, Tunisia.
Curr Res Toxicol ; 6: 100153, 2024.
Article em En | MEDLINE | ID: mdl-38379847
ABSTRACT
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article