Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7β-hydroxycholesterol-, or 24(S)-hydroxycholesterol: Protective effects of α-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3)

Nury, Thomas; Zarrouk, Amira; Mackrill, John J.; Samadi, Mohammad; Durand, Philippe; Riedinger, Jean-Marc; Doria, Margaux; Véjux, Anne; Limagne, Emeric; Delmas, Dominique; Prost, Michel; Moreau, Thibault; Hammami, Mohamed; Delage-Mourroux, Régis; O’Brien, Nora M.; Lizard, Gérard

doi:10.1016/j.steroids.2015.02.003

Cited by 94 publications

(114 citation statements)

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“…Induction of early apoptosis characterized by phosphatidylserine exposure after treatment with 7KC is a commonly observed phenomenon and has been already described in association to other cell-death mechanisms, such as autophagy in vascular smooth muscle cells [37] and oxiapoptophagy in murine oligodendrocytes [29,38]. Interestingly, 7KC was associated with the process of cell death by necrosis in a range of cell models [39]; however, in none of the assayed conditions it was observed evidence of cells undergoing necrotic process.…”

Section: Resultsmentioning

confidence: 78%

“…Recently, 7KC has been suggested to induce a complex form of cell death, oxiapoptophagy, characterized by reduction of cell proliferation, increased membrane permeability, nucleus condensation, decreased production of nitric oxide and oxidative damage to DNA [28,29]. Few studies have reported experiments with oxysterols in normal cells, however oxysterols do not appear to be toxic at concentrations that would be cytostatic or cytotoxic to cancer cell lines [30].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

Rosa-Fernandes

Stern

Cavaglieri

et al. 2017

Journal of Proteomics

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Section: Resultsmentioning

confidence: 78%

Section: Accepted Manuscriptmentioning

confidence: 99%

7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

Rosa-Fernandes

Stern

Cavaglieri

et al. 2017

Journal of Proteomics

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“…At the moment, only a few natural (α-tocopherol, docosahexaenoic acid, polyphenols) and synthetic (dimethylfumarate) molecules are able to protect against the toxic effects of 7KC as described below. Among these molecules, α-tocopherol is one of the most effective in various cell types, including nerve cells [27,34,35,36]. Its main function is to trap lipid peroxyl radicals (LOO • ) by preventing the propagation of lipid peroxidation [37,38,39].…”

Section: Introductionmentioning

confidence: 99%

“…These effects of α-tocopherol were not observed with γ-tocopherol in A7R5 rat smooth muscle cells [41]. α-Tocopherol has also been shown to inhibit oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY), the complex mode of cell death induced not only by 7KC, but also by 7β-hydroxycholesterol and 24S-hydroxycholesterol [35,42]. In 158N murine oligodendrocytes, oxiapoptophagy is also inhibited by dimethyl fumarate (DMF), the active compound of Tecfidera/BG12 used in the treatment of the relapsing-remitting form of MS [43].…”

Section: Introductionmentioning

confidence: 99%

“…Indicaxanthin, a bioactive pigment from cactus pear fruit, has also been shown to prevent 7KC-induced cell death in different cell types [47,48,49]. In 158N cells and SK-N-BE neuronal cells, the toxic effects of 7KC are also strongly inhibited by docosahexaenoic acid (DHA, C22:6 n-3), which is present at high levels in oily fish, such as sardines [35,36]. …”

Section: Introductionmentioning

confidence: 99%

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Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

Debbabi

Nury

Zarrouk

et al. 2016

IJMS

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Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

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Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

Sottero

Leonarduzzi

Testa

et al. 2018

Euro J Lipid Sci & Tech

102

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Non‐enzymatic and enzymatic oxidation of lipids has long been a primary issue in human pathophysiology, with special emphasis on diet‐ and nutrition‐related aspects. While there is no doubt that the n‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid, exert anti‐inflammatory, inflammation resolving, and immunomodulatory effects in different model systems, their non‐enzymatic oxidation during food storage and cooking, as well as during gastrointestinal digestion, can give rise to excessive amounts of quite reactive aldehydic end‐products, in particular 4‐hydroxyhexenal. However, the non‐enzymatic oxidation of n‐6 PUFAs is, in principle, far more harmful, not least because one of its main end‐products, 4‐hydroxynonenal, has been shown to be associated with the progression of a number of human diseases. Several cholesterol oxidation products, known as oxysterols, are also of primary nutritional importance; these can be generated in the human body through both enzymatic and non‐enzymatic reactions, but may also be present in the diet in excessive amounts due to the autoxidation of cholesterol‐containing foods. Their potential contribution to the pathogenesis and progression of human diseases in which hypercholesterolemia is a primary risk factor, such as atheroclerosis, Alzheimer's disease, and some forms of cancers, has been unanimously recognized. Practical Applications: This review highlights the importance of certain lipid oxidation products, namely 4‐hydroxyalkenals and oxysterols, in the modulation of processes fundamental to human health and disease. The observations and facts reviewed here underline the need to carefully consider the pros and cons of the dietary intake and metabolic fate of n‐3 PUFA, n‐6 PUFA, and cholesterol, when producing, storing, and processing lipid‐containing food. Lipid oxidation is a common process that occurs through both enzymatic and non‐enzymatic reactions. It is responsible for the formation of several compounds, including polyunsaturated fatty acid (PUFA)‐derived 4‐hydroxyalkenals and cholesterol oxidation products, namely oxysterols. Depending on their concentrations, these molecules possess physiopathological properties involved in cell viability and function. At high concentrations, such as those resulting from intense oxidative stress or excessive fatty food intake, they are associated to the onset of many diseases. A correct diet regimen, improved food processing and storage, and suitable antioxidant supplementation, should be implemented to counteract promotion of disease development by excess oxidized lipids. (HHE, 4‐hydroxyhexenal; HNE, 4‐hydroxynonenal; ROS, reactive oxygen species).

show abstract

Induction of oxiapoptophagy on 158N murine oligodendrocytes treated by 7-ketocholesterol-, 7β-hydroxycholesterol-, or 24(S)-hydroxycholesterol: Protective effects of α-tocopherol and docosahexaenoic acid (DHA; C22:6 n-3)

Cited by 94 publications

References 67 publications

7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

7-Ketocholesterol overcomes drug resistance in chronic myeloid leukemia cell lines beyond MDR1 mechanism

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

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