Bibliographic Details
| 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 |
| Authors: |
Aline Yammine, Imen Ghzaiel, Vivien Pires, Amira Zarrouk, Omar Kharoubi, Hélène Greige-Gerges, Lizette Auezova, Gérard Lizard, Anne Vejux |
| Source: |
Current Research in Toxicology, Vol 6, Iss , Pp 100153- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Toxicology. Poisons |
| Subject Terms: |
7-ketocholesterol, α-tocopherol, Eicosapentaenoic acid, α-linolenic acid, Oleic acid, glutathione peroxidase, Toxicology. Poisons, RA1190-1270 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2666-027X |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2666027X24000069; https://doaj.org/toc/2666-027X |
| DOI: |
10.1016/j.crtox.2024.100153 |
| Access URL: |
https://doaj.org/article/16ff6ffe11fd4d219d22fc7ddaa205b3 |
| Accession Number: |
edsdoj.16ff6ffe11fd4d219d22fc7ddaa205b3 |
| Database: |
Directory of Open Access Journals |
