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7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.
Imen Ghzaiel; Khouloud Sassi; Amira Zarrouk; Thomas Nury; Mohamed Ksila; Valerio Leoni; Balkiss Bouhaouala-Zahar; Sonia Hammami; Mohamed Hammami; John J. Mackrill; Mohammad Samadi; Taoufik Ghrairi; Anne Vejux; Gérard Lizard. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19. The Journal of Steroid Biochemistry and Molecular Biology 2021, 212, 105939 .
AMA StyleImen Ghzaiel, Khouloud Sassi, Amira Zarrouk, Thomas Nury, Mohamed Ksila, Valerio Leoni, Balkiss Bouhaouala-Zahar, Sonia Hammami, Mohamed Hammami, John J. Mackrill, Mohammad Samadi, Taoufik Ghrairi, Anne Vejux, Gérard Lizard. 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19. The Journal of Steroid Biochemistry and Molecular Biology. 2021; 212 ():105939.
Chicago/Turabian StyleImen Ghzaiel; Khouloud Sassi; Amira Zarrouk; Thomas Nury; Mohamed Ksila; Valerio Leoni; Balkiss Bouhaouala-Zahar; Sonia Hammami; Mohamed Hammami; John J. Mackrill; Mohammad Samadi; Taoufik Ghrairi; Anne Vejux; Gérard Lizard. 2021. "7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19." The Journal of Steroid Biochemistry and Molecular Biology 212, no. : 105939.
The Mediterranean diet is a central element of a healthy lifestyle, where polyphenols play a key role due to their anti-oxidant properties, and for some of them, as nutripharmacological compounds capable of preventing a number of diseases, including cancer. Due to the high prevalence of intestinal cancer (ranking second in causing morbidity and mortality), this review is focused on the beneficial effects of selected dietary phytophenols, largely present in Mediterranean cooking: apigenin, curcumin, epigallocatechin gallate, quercetin-rutine, and resveratrol. The role of the Mediterranean diet in the prevention of colorectal cancer and future perspectives are discussed in terms of food polyphenol content, the effectiveness, the plasma level, and the importance of other factors, such as the polyphenol metabolites and the influence of the microbiome. Perspectives are discussed in terms of microbiome-dependency of the brain-second brain axis. The emergence of polyphenol formulations may strengthen the efficiency of the Mediterranean diet in the prevention of cancer.
Aline Yammine; Amira Namsi; Dominique Vervandier-Fasseur; John Mackrill; Gérard Lizard; Norbert Latruffe. Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer. Molecules 2021, 26, 3483 .
AMA StyleAline Yammine, Amira Namsi, Dominique Vervandier-Fasseur, John Mackrill, Gérard Lizard, Norbert Latruffe. Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer. Molecules. 2021; 26 (12):3483.
Chicago/Turabian StyleAline Yammine; Amira Namsi; Dominique Vervandier-Fasseur; John Mackrill; Gérard Lizard; Norbert Latruffe. 2021. "Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer." Molecules 26, no. 12: 3483.
Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7β-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer’s disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7β-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7β-hydroxycholesterol.
T. Nury; A. Yammine; I. Ghzaiel; K. Sassi; A. Zarrouk; F. Brahmi; M. Samadi; S. Rup-Jacques; D. Vervandier-Fasseur; J.P. Pais de Barros; V. Bergas; S. Ghosh; M. Majeed; A. Pande; A. Atanasov; S. Hammami; J. Mackrill; B. Nasser; P. Andreoletti; M. Cherkaoui-Malki; A. Vejux; G. Lizard. Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases. Ageing Research Reviews 2021, 68, 101324 .
AMA StyleT. Nury, A. Yammine, I. Ghzaiel, K. Sassi, A. Zarrouk, F. Brahmi, M. Samadi, S. Rup-Jacques, D. Vervandier-Fasseur, J.P. Pais de Barros, V. Bergas, S. Ghosh, M. Majeed, A. Pande, A. Atanasov, S. Hammami, J. Mackrill, B. Nasser, P. Andreoletti, M. Cherkaoui-Malki, A. Vejux, G. Lizard. Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases. Ageing Research Reviews. 2021; 68 ():101324.
Chicago/Turabian StyleT. Nury; A. Yammine; I. Ghzaiel; K. Sassi; A. Zarrouk; F. Brahmi; M. Samadi; S. Rup-Jacques; D. Vervandier-Fasseur; J.P. Pais de Barros; V. Bergas; S. Ghosh; M. Majeed; A. Pande; A. Atanasov; S. Hammami; J. Mackrill; B. Nasser; P. Andreoletti; M. Cherkaoui-Malki; A. Vejux; G. Lizard. 2021. "Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases." Ageing Research Reviews 68, no. : 101324.
Multiple sclerosis is an autoimmune disease that affects the central nervous system. Dysfunction of the immune system leads to lesions that cause motor, sensory, cognitive, visual and/or sphincter disturbances. In the long term, these disorders can progress towards an irreversible handicap. The diagnosis takes time because there are no specific criteria to diagnose multiple sclerosis. To realize the diagnosis, a combination of clinical, biological, and radiological arguments is therefore required. Hence, there is a need to identify multiple sclerosis biomarkers. Some biomarkers target immunity through the detection of oligoclonal bands, the measurement of the IgG index and cytokines. During the physiopathological process, the blood-brain barrier can be broken, and this event can be identified by measuring metalloproteinase activity and diffusion of gadolinium in the brain by magnetic resonance imaging. Markers of demyelination and of astrocyte and microglial activity may also be of interest as well as markers of neuronal damage and mitochondrial status. The measurement of different lipids in the plasma and cerebrospinal fluid can also provide suitable information. These different lipids include fatty acids, fatty acid peroxidation products, phospholipids as well as oxidized derivatives of cholesterol (oxysterols). Oxysterols could constitute new biomarkers providing information on the form of multiple sclerosis, the outcome of the disease and the answer to treatment.
Anne Vejux; Imen Ghzaiel; Thomas Nury; Vincent Schneider; Karine Charrière; Randa Sghaier; Amira Zarrouk; Valerio Leoni; Thibault Moreau; Gérard Lizard. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy. The Journal of Steroid Biochemistry and Molecular Biology 2021, 210, 105870 .
AMA StyleAnne Vejux, Imen Ghzaiel, Thomas Nury, Vincent Schneider, Karine Charrière, Randa Sghaier, Amira Zarrouk, Valerio Leoni, Thibault Moreau, Gérard Lizard. Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy. The Journal of Steroid Biochemistry and Molecular Biology. 2021; 210 ():105870.
Chicago/Turabian StyleAnne Vejux; Imen Ghzaiel; Thomas Nury; Vincent Schneider; Karine Charrière; Randa Sghaier; Amira Zarrouk; Valerio Leoni; Thibault Moreau; Gérard Lizard. 2021. "Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy." The Journal of Steroid Biochemistry and Molecular Biology 210, no. : 105870.
The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.
Aline Yammine; Amira Zarrouk; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; John J. Mackrill; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases. Cells 2020, 9, 2346 .
AMA StyleAline Yammine, Amira Zarrouk, Thomas Nury, Anne Vejux, Norbert Latruffe, Dominique Vervandier-Fasseur, Mohammad Samadi, John J. Mackrill, Hélène Greige-Gerges, Lizette Auezova, Gérard Lizard. Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases. Cells. 2020; 9 (11):2346.
Chicago/Turabian StyleAline Yammine; Amira Zarrouk; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; John J. Mackrill; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. 2020. "Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases." Cells 9, no. 11: 2346.
Zinc oxide nanoparticles (ZnO NPs) possess huge application potential. However, the toxicity of ZnO NPs is a great cause of concern. Indeed, ZnO NPs have been found to cause neurotoxicity. As microglial dysfunctions have been linked to the neurotoxic potential of NPs, the physico-chemical properties of ZnO NPs were determined and their cytotoxic effects were characterised on murine microglial BV-2 cells. In-house prepared and meticulously characterised ZnO NPs exhibited narrow size distribution with an average size of around 20 nm and a zeta potential at physiological pH around 24 mV. ZnO NPs did not exhibit aggregation in the cell culture medium. When microglial BV-2 cells were exposed for 6 and 24 h to ZnO NPs (5, 10, 20, 40, and 80 μg/mL), several cell damages were observed. Cellular accumulation of NPs in microglial BV-2 cells was associated with cell growth inhibition and cell death induction, measured by the trypan blue exclusion and MTT assays. Mitochondrial dysfunction and lysosomal alteration were associated with increased plasma membrane permeability measured by staining with DiOC6(3), acridine orange, and propidium iodide, respectively. In addition, an accumulation of reactive oxygen species (ROS) was detected after staining with dihydroethidium and dihydrorhodamine 123. No apoptotic features were present: no cells with condensed and/or fragmented nuclei (Hoechst staining) characteristic of apoptotic cells, absence of subG1 cells, absence of caspase-3 cleavage, and PARP fragmentation. With ZnO NPs (80 μg/mL), with the annexin V/propidium iodide (PI) assay, few apoptotic cells (annexin V+/PI− cells) were detected whereas (annexin V+/PI+ cells) evocating necrotic cells were mainly identified. No modification of the cells in the different phases of the cell cycle was found. Altogether, our data show that ZnO NPs induce a non-apoptotic mode of cell death associated with an accumulation of ROS, mitochondrial, and lysosomal dysfunction and plasma membrane damages in microglial BV-2 cells. Graphical abstract
Sudhakaran Sruthi; Thomas Nury; Nadine Millot; Gérard Lizard. Evidence of a non-apoptotic mode of cell death in microglial BV-2 cells exposed to different concentrations of zinc oxide nanoparticles. Environmental Science and Pollution Research 2020, 28, 12500 -12520.
AMA StyleSudhakaran Sruthi, Thomas Nury, Nadine Millot, Gérard Lizard. Evidence of a non-apoptotic mode of cell death in microglial BV-2 cells exposed to different concentrations of zinc oxide nanoparticles. Environmental Science and Pollution Research. 2020; 28 (10):12500-12520.
Chicago/Turabian StyleSudhakaran Sruthi; Thomas Nury; Nadine Millot; Gérard Lizard. 2020. "Evidence of a non-apoptotic mode of cell death in microglial BV-2 cells exposed to different concentrations of zinc oxide nanoparticles." Environmental Science and Pollution Research 28, no. 10: 12500-12520.
Oxysterols are oxidized forms of cholesterol generated from cholesterol by auto‐oxidation, enzymatic processes, or both. Some of them (7‐ketocholesterol, 7β‐hydroxycholesterol and 24(S)‐hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells and nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of ROS, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation. Apoptosis is associated with activation of the mitochondrial pathway, opening of the mitochondrial permeability pore, loss of mitochondrial membrane potential, caspase‐3 activation, PARP degradation, nuclear condensation and/or fragmentation. Autophagy is characterized by autophagic vacuoles revealed by monodansylcadaverine staining and transmission electron microscopy, plus increased ratio of LC‐3II/LC‐3I. In addition, morphological, topographical and functional changes of the peroxisome are observed.
Thomas Nury; Amira Zarrouk; Aline Yammine; John J. Mackrill; Anne Vejux; Gérard Lizard. Oxiapoptophagy: A type of cell death induced by some oxysterols. British Journal of Pharmacology 2020, 178, 3115 -3123.
AMA StyleThomas Nury, Amira Zarrouk, Aline Yammine, John J. Mackrill, Anne Vejux, Gérard Lizard. Oxiapoptophagy: A type of cell death induced by some oxysterols. British Journal of Pharmacology. 2020; 178 (16):3115-3123.
Chicago/Turabian StyleThomas Nury; Amira Zarrouk; Aline Yammine; John J. Mackrill; Anne Vejux; Gérard Lizard. 2020. "Oxiapoptophagy: A type of cell death induced by some oxysterols." British Journal of Pharmacology 178, no. 16: 3115-3123.
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 DiOC6(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.
Aline Yammine; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. 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. Molecules 2020, 25, 2296 .
AMA StyleAline Yammine, Thomas Nury, Anne Vejux, Norbert Latruffe, Dominique Vervandier-Fasseur, Mohammad Samadi, Hélène Greige-Gerges, Lizette Auezova, Gérard Lizard. 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. Molecules. 2020; 25 (10):2296.
Chicago/Turabian StyleAline Yammine; Thomas Nury; Anne Vejux; Norbert Latruffe; Dominique Vervandier-Fasseur; Mohammad Samadi; Hélène Greige-Gerges; Lizette Auezova; Gérard Lizard. 2020. "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." Molecules 25, no. 10: 2296.
Many parameters can influence the chemical profiles and the biological activities of seed oils. It was therefore of interest to study Algerian seed oils, whose caharacteristics are not well known. So, the physicochemical properties and nutrient profiles (fatty acids, phytosterols, polyphenols) of seed oils from Pistacia lentiscus L. (PL), Opuntia ficus-indica (L.) mill. (OFI), and Argania spinosa L. Skeels (AS) were determined. The antioxidant and antimicrobial activities of the oils were also characterized. The physicochemical parameters of the oils are closely related to the standard values. PL oil is distinguished by its high content of pigments. AS and OFI oils were dominated by linoleic acid, at 39.1 ± 0.5 and 55.8 ± 0.6%, respectively, while the oleic acid (41.2 ± 0.4%) was the major fatty acid in the oil of PL. The analysis of phytosterol levels showed that β-sitosterol was present in high amounts in the three oils, of 387.44 ± 3.04, 87.92 ± 0.72 and 58.79 ± 1.19 mg/100 g of oil in OFI, AS and PL oils, respectively. The characterization of phenolics revealed only the presence of protocatechuic acid in the PL oil and p-coumaric and t-cinnamic acids in AS oil. The antioxidant activity was evaluated by using the phosphomolybdate assay and the scavenger activity of the DPPH• radical. PL and OFI oils showed the highest antioxidant capacity compared with AS. Very weak antibacterial and antifungal effects, evaluated against four bacterial and six fungal strains, were found. Given the chemical characteristics and antioxidant properties of Algerian PL, OFI and AS seed oils, our results highlight the potential benefit of these oils for human health.
Fatiha Brahmi; Souhila Haddad; Kenza Bouamara; Drifa Yalaoui-Guellal; Emmanuelle Prost-Camus; Jean-Paul Pais de Barros; Michel Prost; Atanas G. Atanasov; Khodir Madani; Lila Boulekbache-Makhlouf; Gérard Lizard. Comparison of chemical composition and biological activities of Algerian seed oils of Pistacia lentiscus L., Opuntia ficus indica (L.) mill. and Argania spinosa L. Skeels. Industrial Crops and Products 2020, 151, 112456 .
AMA StyleFatiha Brahmi, Souhila Haddad, Kenza Bouamara, Drifa Yalaoui-Guellal, Emmanuelle Prost-Camus, Jean-Paul Pais de Barros, Michel Prost, Atanas G. Atanasov, Khodir Madani, Lila Boulekbache-Makhlouf, Gérard Lizard. Comparison of chemical composition and biological activities of Algerian seed oils of Pistacia lentiscus L., Opuntia ficus indica (L.) mill. and Argania spinosa L. Skeels. Industrial Crops and Products. 2020; 151 ():112456.
Chicago/Turabian StyleFatiha Brahmi; Souhila Haddad; Kenza Bouamara; Drifa Yalaoui-Guellal; Emmanuelle Prost-Camus; Jean-Paul Pais de Barros; Michel Prost; Atanas G. Atanasov; Khodir Madani; Lila Boulekbache-Makhlouf; Gérard Lizard. 2020. "Comparison of chemical composition and biological activities of Algerian seed oils of Pistacia lentiscus L., Opuntia ficus indica (L.) mill. and Argania spinosa L. Skeels." Industrial Crops and Products 151, no. : 112456.
Neurodegenerative diseases, particularly Parkinson’s and Alzheimer’s, have common features: protein accumulation, cell death with mitochondrial involvement and oxidative stress. Patients are treated to cure the symptoms, but the treatments do not target the causes; so, the disease is not stopped. It is interesting to look at the side of nutrition which could help prevent the first signs of the disease or slow its progression in addition to existing therapeutic strategies. Lipids, whether in the form of vegetable or animal oils or in the form of fatty acids, could be incorporated into diets with the aim of preventing neurodegenerative diseases. These different lipids can inhibit the cytotoxicity induced during the pathology, whether at the level of mitochondria, oxidative stress or apoptosis and inflammation. The conclusions of the various studies cited are oriented towards the preventive use of oils or fatty acids. The future of these lipids that can be used in therapy/prevention will undoubtedly involve a better delivery to the body and to the brain by utilizing lipid encapsulation.
Thomas Nury; Gérard Lizard; Anne Vejux. Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection. International Journal of Molecular Sciences 2020, 21, 2501 .
AMA StyleThomas Nury, Gérard Lizard, Anne Vejux. Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection. International Journal of Molecular Sciences. 2020; 21 (7):2501.
Chicago/Turabian StyleThomas Nury; Gérard Lizard; Anne Vejux. 2020. "Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection." International Journal of Molecular Sciences 21, no. 7: 2501.
Several series of natural polyphenols are described for their biological and therapeutic potential. Natural stilbenoid polyphenols, such as trans-resveratrol, pterostilbene and piceatannol are well-known for their numerous biological activities. However, their moderate bio-availabilities, especially for trans-resveratrol, prompted numerous research groups to investigate innovative and relevant synthetic resveratrol derivatives. This review is focused on isosteric resveratrol analogs aza-stilbenes and azo-stilbenes in which the C=C bond between both aromatic rings was replaced with C=N or N=N bonds, respectively. In each series, synthetic ways will be displayed, and structural sights will be highlighted and compared with those of resveratrol. The biological activities of some of these molecules will be presented as well as their potential therapeutic applications. In some cases, structure-activity relationships will be discussed.
Gérard Lizard; Norbert Latruffe; Dominique Vervandier-Fasseur. Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol. Molecules 2020, 25, 605 .
AMA StyleGérard Lizard, Norbert Latruffe, Dominique Vervandier-Fasseur. Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol. Molecules. 2020; 25 (3):605.
Chicago/Turabian StyleGérard Lizard; Norbert Latruffe; Dominique Vervandier-Fasseur. 2020. "Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol." Molecules 25, no. 3: 605.
In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.
Thomas Nury; Margaux Doria; Gérard Lizard; Anne Vejux. Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model. International Journal of Molecular Sciences 2020, 21, 641 .
AMA StyleThomas Nury, Margaux Doria, Gérard Lizard, Anne Vejux. Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model. International Journal of Molecular Sciences. 2020; 21 (2):641.
Chicago/Turabian StyleThomas Nury; Margaux Doria; Gérard Lizard; Anne Vejux. 2020. "Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model." International Journal of Molecular Sciences 21, no. 2: 641.
Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer’s disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC). These observations led to the demonstration that 7KC and 7β-OHC alter the biogenesis and activity of peroxisomes in glial and microglial cells. In X-ALD, AD, and MS, it is suggested that 7KC and 7β-OHC affecting the peroxisome, and which also induce mitochondrial dysfunctions, oxidative stress, and inflammation, could promote neurodegeneration. Consequently, the study of oxisome in peroxisomopathies, AD and MS, could help to better understand the pathophysiology of these diseases to identify therapeutic targets for effective treatments.
Thomas Nury; Aline Yammine; Franck Menetrier; Amira Zarrouk; Anne Vejux; Gérard Lizard. 7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration. Advances in Experimental Medicine and Biology 2020, 1299, 31 -41.
AMA StyleThomas Nury, Aline Yammine, Franck Menetrier, Amira Zarrouk, Anne Vejux, Gérard Lizard. 7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration. Advances in Experimental Medicine and Biology. 2020; 1299 ():31-41.
Chicago/Turabian StyleThomas Nury; Aline Yammine; Franck Menetrier; Amira Zarrouk; Anne Vejux; Gérard Lizard. 2020. "7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration." Advances in Experimental Medicine and Biology 1299, no. : 31-41.
Oxidative stress and mitochondrial dysfunction contribute to the pathogenesis of neurodegenerative diseases and favor lipid peroxidation, leading to increased levels of 7β-hydroxycholesterol (7β-OHC) which induces oxiapoptophagy (OXIdative stress, APOPTOsis, autoPHAGY). The cytoprotective effects of dimethylfumarate (DMF), used in the treatment of relapsing remitting multiple sclerosis and of monomethylfumarate (MMF), its main metabolite, were evaluated on murine oligodendrocytes 158 N exposed to 7β-OHC (50 μM, 24 h) with or without DMF or MMF (25 μM). The activity of 7β-OHC in the presence or absence DMF or MMF was evaluated on several parameters: cell adhesion; plasma membrane integrity measured with propidium iodide (PI), trypan blue and fluoresceine diacetate (FDA) assays; LDH activity; antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)); generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation products (carbonylated proteins (CPs)); reactive oxygen species (ROS) overproduction conducted with DHE and DHR123. The effect on mitochondria was determined with complementary criteria: measurement of succinate dehydrogenase activity, evaluation of mitochondrial potential (ΔΨm) and mitochondrial superoxide anions (O2●-) production using DiOC6(3) and MitoSOX, respectively; quantification of mitochondrial mass with Mitotracker Red, and of cardiolipins and organic acids. The effects on mitochondrial and peroxisomal ultrastructure were determined by transmission electron microscopy. Intracellular sterol and fatty acid profiles were determined. Apoptosis and autophagy were characterized by staining with Hoechst 33,342, Giemsa and acridine orange, and with antibodies raised against caspase-3 and LC3. DMF and MMF attenuate 7β-OHC-induced cytotoxicity: cell growth inhibition; decreased cell viability; mitochondrial dysfunction (decrease of succinate dehydrogenase activity, loss of ΔΨm, increase of mitochondrial O2●- production, alteration of the tricarboxilic acid (TCA) cycle, and cardiolipins content); oxidative stress induction (ROS overproduction, alteration of GPx, CAT, and SOD activities, increased levels of MDA, CDs, and CPs); changes in fatty acid and cholesterol metabolism; and cell death induction (caspase-3 cleavage, activation of LC3-I in LC3-II). Ultrastructural alterations of mitochondria and peroxisomes were prevented. These results demonstrate that DMF and MMF prevent major dysfunctions associated with neurodegenerative diseases: oxidative stress, mitochondrial dysfunction, apoptosis and autophagy.
Randa Sghaier; Thomas Nury; Valerio Leoni; Claudio Caccia; Jean-Paul Pais De Barros; Ameur Cherif; Anne Vejux; Thibault Moreau; Khalifa Limem; Mohammad Samadi; John J. Mackrill; Ahmed Masmoudi; Gérard Lizard; Amira Zarrouk. Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol. The Journal of Steroid Biochemistry and Molecular Biology 2019, 194, 105432 .
AMA StyleRanda Sghaier, Thomas Nury, Valerio Leoni, Claudio Caccia, Jean-Paul Pais De Barros, Ameur Cherif, Anne Vejux, Thibault Moreau, Khalifa Limem, Mohammad Samadi, John J. Mackrill, Ahmed Masmoudi, Gérard Lizard, Amira Zarrouk. Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol. The Journal of Steroid Biochemistry and Molecular Biology. 2019; 194 ():105432.
Chicago/Turabian StyleRanda Sghaier; Thomas Nury; Valerio Leoni; Claudio Caccia; Jean-Paul Pais De Barros; Ameur Cherif; Anne Vejux; Thibault Moreau; Khalifa Limem; Mohammad Samadi; John J. Mackrill; Ahmed Masmoudi; Gérard Lizard; Amira Zarrouk. 2019. "Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol." The Journal of Steroid Biochemistry and Molecular Biology 194, no. : 105432.
M.T. Rodriguez-Estrada; V. Cardenia; M. Poirot; L. Iuliano; G. Lizard. Oxysterols and sterols: From lipidomics to food sciences. The Journal of Steroid Biochemistry and Molecular Biology 2019, 196, 105515 .
AMA StyleM.T. Rodriguez-Estrada, V. Cardenia, M. Poirot, L. Iuliano, G. Lizard. Oxysterols and sterols: From lipidomics to food sciences. The Journal of Steroid Biochemistry and Molecular Biology. 2019; 196 ():105515.
Chicago/Turabian StyleM.T. Rodriguez-Estrada; V. Cardenia; M. Poirot; L. Iuliano; G. Lizard. 2019. "Oxysterols and sterols: From lipidomics to food sciences." The Journal of Steroid Biochemistry and Molecular Biology 196, no. : 105515.
Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties. They are powerful inducers of oxidative stress, inducing dysfunction of organelles (mitochondria, lysosomes and peroxisomes) that can cause cell death. These molecules are often identified in increased amounts in common pathological states such as cardiovascular diseases, certain eye conditions, neurodegenerative disorders and inflammatory bowel diseases. To oppose the cytotoxic effects of these molecules, it is important to know their biological activities and the signaling pathways they affect. Numerous cell models of the vascular wall, eye, brain, and digestive tract have been used. Currently, to counter the cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol, natural molecules and oils, often associated with the Mediterranean diet, as well as synthetic molecules, have proved effective in vitro. Bioremediation approaches and the use of functionalized nanoparticles are also promising. At the moment, invertebrate and vertebrate models are mainly used to evaluate the metabolism and the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol. The most frequently used models are mice, rats and rabbits. In order to cope with the difficulty of transferring the results obtained in animals to humans, the development of in vitro alternative methods such as organ/body-on-a-chip based on microfluidic technology are hopeful integrative approaches.
Anne Vejux; Dehbia Abed-Vieillard; Khadija Hajji; Amira Zarrouk; John J. Mackrill; Shubhrima Ghosh; Thomas Nury; Aline Yammine; Mohamed Zaibi; Wafa Mihoubi; Habiba Bouchab; Boubker Nasser; Yael Grosjean; Gérard Lizard. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity. Biochemical Pharmacology 2019, 173, 113648 .
AMA StyleAnne Vejux, Dehbia Abed-Vieillard, Khadija Hajji, Amira Zarrouk, John J. Mackrill, Shubhrima Ghosh, Thomas Nury, Aline Yammine, Mohamed Zaibi, Wafa Mihoubi, Habiba Bouchab, Boubker Nasser, Yael Grosjean, Gérard Lizard. 7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity. Biochemical Pharmacology. 2019; 173 ():113648.
Chicago/Turabian StyleAnne Vejux; Dehbia Abed-Vieillard; Khadija Hajji; Amira Zarrouk; John J. Mackrill; Shubhrima Ghosh; Thomas Nury; Aline Yammine; Mohamed Zaibi; Wafa Mihoubi; Habiba Bouchab; Boubker Nasser; Yael Grosjean; Gérard Lizard. 2019. "7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity." Biochemical Pharmacology 173, no. : 113648.
Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10−14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.
Amira Namsi; Thomas Nury; Amira. S. Khan; Jérôme Leprince; David Vaudry; Claudio Caccia; Valerio Leoni; Atanas G. Atanasov; Marie-Christine Tonon; Olfa Masmoudi-Kouki; Gérard Lizard; Nury; Khan; Masmoudi- Kouki. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles. Molecules 2019, 24, 3310 .
AMA StyleAmira Namsi, Thomas Nury, Amira. S. Khan, Jérôme Leprince, David Vaudry, Claudio Caccia, Valerio Leoni, Atanas G. Atanasov, Marie-Christine Tonon, Olfa Masmoudi-Kouki, Gérard Lizard, Nury, Khan, Masmoudi- Kouki. Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles. Molecules. 2019; 24 (18):3310.
Chicago/Turabian StyleAmira Namsi; Thomas Nury; Amira. S. Khan; Jérôme Leprince; David Vaudry; Claudio Caccia; Valerio Leoni; Atanas G. Atanasov; Marie-Christine Tonon; Olfa Masmoudi-Kouki; Gérard Lizard; Nury; Khan; Masmoudi- Kouki. 2019. "Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles." Molecules 24, no. 18: 3310.
The immune response is essential to protect organisms from infection and an altered self. An organism’s overall metabolic status is now recognized as an important and long-overlooked mediator of immunity and has spurred new explorations of immune-related metabolic abnormalities. Peroxisomes are essential metabolic organelles with a central role in the synthesis and turnover of complex lipids and reactive species. Peroxisomes have recently been identified as pivotal regulators of immune functions and inflammation in the development and during infection, defining a new branch of immunometabolism. This review summarizes the current evidence that has helped to identify peroxisomes as central regulators of immunity and highlights the peroxisomal proteins and metabolites that have acquired relevance in human pathologies for their link to the development of inflammation, neuropathies, aging and cancer. This review then describes how peroxisomes govern immune signaling strategies such as phagocytosis and cytokine production and their relevance in fighting bacterial and viral infections. The mechanisms by which peroxisomes either control the activation of the immune response or trigger cellular metabolic changes that activate and resolve immune responses are also described.
Francesca Di Cara; Pierre Andreoletti; Doriane Trompier; Anne Vejux; Margret H. Bülow; Julia Sellin; Gérard Lizard; Mustapha Cherkaoui-Malki; Stéphane Savary. Peroxisomes in Immune Response and Inflammation. International Journal of Molecular Sciences 2019, 20, 3877 .
AMA StyleFrancesca Di Cara, Pierre Andreoletti, Doriane Trompier, Anne Vejux, Margret H. Bülow, Julia Sellin, Gérard Lizard, Mustapha Cherkaoui-Malki, Stéphane Savary. Peroxisomes in Immune Response and Inflammation. International Journal of Molecular Sciences. 2019; 20 (16):3877.
Chicago/Turabian StyleFrancesca Di Cara; Pierre Andreoletti; Doriane Trompier; Anne Vejux; Margret H. Bülow; Julia Sellin; Gérard Lizard; Mustapha Cherkaoui-Malki; Stéphane Savary. 2019. "Peroxisomes in Immune Response and Inflammation." International Journal of Molecular Sciences 20, no. 16: 3877.
Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β- hydroxycholesterol (7β-OHC). It is therefore important to study the ability of 7β-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7β-OHC activities were determined using different criteria: cell adhesion; plasma membrane integrity; redox status. The impact on mitochondria was characterized by the measurement of transmembrane mitochondrial potential (ΔΨm), reactive oxygen species (ROS) overproduction, mitochondrial mass, quantification of cardiolipins and organic acids. Sterols and fatty acids were also quantified. Cell death (apoptosis, autophagy) was characterized by the numeration of apoptotic cells, caspase-3 activation, identification of autophagic vesicles, and activation of LC3-I into LC3-II. Biotin attenuates 7β-OHC-induced cytotoxicity: loss of cell adhesion was reduced; antioxidant activities were normalized. ROS overproduction, protein and lipid oxidation products were decreased. Biotin partially restores mitochondrial functions: attenuation of the loss of ΔΨm; reduced levels of mitochondrial O2•− overproduction; normalization of cardiolipins and organic acid levels. Biotin also normalizes cholesterol and fatty acid synthesis, and prevents apoptosis and autophagy (oxiapoptophagy). Our data support that biotin, which prevents oligodendrocytes damages, could be useful in the treatment of neurodegeneration and demyelination. Numerous side effects are induced by 7β-hydroxycholesterol on murine oligodendrocytes (158-N cells): oxidative stress, mitochondrial dysfunction, alteration of lipid metabolism (fatty acids, cholesterol), apoptosis and autophagy. These different side effects contribute to induce a complex mode of cell death: oxiapoptophagy (OXIdative stress + APOPTOsis + autoPHAGY). Of note, these different side effects often observed in neurodegenerative diseases including demyelinating diseases, are strongly attenuated by biotin (vitamin B8/H), which pass the blood brain barrier and which is a ubiquitous coenzyme in human cells.
Randa Sghaier; Amira Zarrouk; Thomas Nury; Ilham Badreddine; Nora O’Brien; John J. Mackrill; Anne Vejux; Mohammad Samadi; Boubker Nasser; Claudio Caccia; Valerio Leoni; Thibault Moreau; Mustapha Cherkaoui-Malki; Ahmed Masmoudi; Gérard Lizard. Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes. Free Radical Research 2019, 53, 535 -561.
AMA StyleRanda Sghaier, Amira Zarrouk, Thomas Nury, Ilham Badreddine, Nora O’Brien, John J. Mackrill, Anne Vejux, Mohammad Samadi, Boubker Nasser, Claudio Caccia, Valerio Leoni, Thibault Moreau, Mustapha Cherkaoui-Malki, Ahmed Masmoudi, Gérard Lizard. Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes. Free Radical Research. 2019; 53 (5):535-561.
Chicago/Turabian StyleRanda Sghaier; Amira Zarrouk; Thomas Nury; Ilham Badreddine; Nora O’Brien; John J. Mackrill; Anne Vejux; Mohammad Samadi; Boubker Nasser; Claudio Caccia; Valerio Leoni; Thibault Moreau; Mustapha Cherkaoui-Malki; Ahmed Masmoudi; Gérard Lizard. 2019. "Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes." Free Radical Research 53, no. 5: 535-561.
Steroidal maleic anhydrides were prepared in one step: lithocholic, chenodeoxicholic, deoxicholic, ursocholic, and hyodeoxicholic acid derivatives. Their capability to induce cell death was studied on C6 rat glioma cells, and 7β-hydroxycholesterol was used as positive cytotoxic control. The highest cytotoxicity was observed with lithocholic and chenodeoxicholic acid derivatives (23-(4-methylfuran-2,5-dione)-3α-hydroxy-24-nor-5β-cholane (compound 1a), and 23-(4-methylfuran-2,5-dione)-3α,7α-dihydroxy-24-nor-5β-cholane (compound 1b), respectively), which induce a non-apoptotic mode of cell death associated with mitochondrial membrane potential loss and reactive oxygen species overproduction. No cells with condensed and/or fragmented nuclei, no PARP degradation and no cleaved-caspase-3, which are apoptotic criteria, were observed. Similar effects were found with 7β-hydroxycholesterol. The cell clonogenic survival assay showed that compound 1b was more cytotoxic than compound 1a and 7β-hydroxycholesterol. Compound 1b and 7β-hydroxycholesterol also induce cell cycle modifications. In addition, compounds 1a and 1b, and 7β-hydroxycholesterol favour the formation of large acidic vacuoles revealed by staining with acridine orange and monodansylcadaverine evocating autophagic vacuoles; they also induce an increased ratio of [LC3-II / LC3-I], and modify the expression of mTOR, Beclin-1, Atg12, and Atg5-Atg12 which is are autophagic criteria. The ratio [LC3-II / LC3-I] is also strongly modified by bafilomycin acting on the autophagic flux. Rapamycin, an autophagic inducer, and 3-methyladenine, an autophagic inhibitor, reduce and increase 7β-hydroxycholesterol-induced cell death, respectively, supporting that 7β-hydroxycholesterol induces survival autophagy. Alpha-tocopherol also strongly attenuates 7β-hydroxycholesterol-induced cell death. However, rapamycin, 3-methyladenine, and α-tocopherol have no effect on compounds 1a and 1b-induced cell death. It is concluded that these compounds trigger a non apoptotic mode of cell death, involving the mitochondria and associated with several characteristics of autophagy.
K. Sassi; T. Nury; A. Zarrouk; R. Sghaier; Ali Khalafi-Nezhad; A. Vejux; M. Samadi; F. Ben Aissa-Fennira; G. Lizard. Induction of a non-apoptotic mode of cell death associated with autophagic characteristics with steroidal maleic anhydrides and 7β-hydroxycholesterol on glioma cells. The Journal of Steroid Biochemistry and Molecular Biology 2019, 191, 105371 .
AMA StyleK. Sassi, T. Nury, A. Zarrouk, R. Sghaier, Ali Khalafi-Nezhad, A. Vejux, M. Samadi, F. Ben Aissa-Fennira, G. Lizard. Induction of a non-apoptotic mode of cell death associated with autophagic characteristics with steroidal maleic anhydrides and 7β-hydroxycholesterol on glioma cells. The Journal of Steroid Biochemistry and Molecular Biology. 2019; 191 ():105371.
Chicago/Turabian StyleK. Sassi; T. Nury; A. Zarrouk; R. Sghaier; Ali Khalafi-Nezhad; A. Vejux; M. Samadi; F. Ben Aissa-Fennira; G. Lizard. 2019. "Induction of a non-apoptotic mode of cell death associated with autophagic characteristics with steroidal maleic anhydrides and 7β-hydroxycholesterol on glioma cells." The Journal of Steroid Biochemistry and Molecular Biology 191, no. : 105371.