scholarly journals N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1826
Author(s):  
Jie Zhou ◽  
Marcia R. Terluk ◽  
Paul J. Orchard ◽  
James C. Cloyd ◽  
Reena V. Kartha
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Specific Effects ◽  
Low Concentrations ◽  
Long Chain ◽  
Chain Fatty Acids

The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.

The effects of fatty acids on pure cultures of rumen bacteria

1973 ◽  
Vol 81 (1) ◽  
pp. 107-112 ◽  
Author(s):  
C. Henderson
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Rumen Bacteria ◽  
Long Chain Fatty Acids ◽  
Selenomonas Ruminantium ◽  
Low Concentrations ◽  
Pure Cultures ◽  
Long Chain ◽  
Chain Fatty Acids

SummaryThe effects of fatty acids, at low concentrations (0–005-O5 g/1), on the growth of seven species of rumen bacteria were examined.Anaerovibrio lipolytica(strain 5 S),Peptostreptococcus elsdenii(type 2),Bacteroides ruminicola46/52 andSelenomonas ruminantium(strain 17) were unaffected by addition of oleic acid to the medium. Growth ofButyrivibrioB 835 was stimulated by low concentrations of oleic (< 0–01 g/1), lauric (< 0–1 g/1) or capric (< 0–1 g/1) acids while higher concentrations of these acids were inhibitory. Myristic, palmitic and stearic acids were inhibitory at all concentrations tested.Ruminococcus4263/1 was inhibited at all concentrations of the six acids. Production of methane by pure cultures ofMethanobacterium ruminantiumwas also inhibited by the additions of long-chain fatty acids. Oleic acid was the most inhibitory of the series of acids. These results are consistent with the reported effects of lipids on rumen function.

Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-α on oligodendrocytes and astrocytes

2012 ◽  
Vol 33 (2) ◽  
pp. 212-228 ◽  
Author(s):  
Mauhamad Baarine ◽  
Kévin Ragot ◽  
Anne Athias ◽  
Thomas Nury ◽  
Zilal Kattan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Long Chain Fatty Acids ◽  
Tnf Α ◽  
Long Chain ◽  
Chain Fatty Acids

Membrane Disruption by Very Long Chain Fatty Acids During Necroptosis

2019 ◽  
Author(s):  
Laura Parisi ◽  
Shahin Sowlati-Hashjin ◽  
Ilyas Berhane ◽  
Kevin Carter ◽  
Jonathan Lovell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Lipid Bilayers ◽  
Membrane Permeabilization ◽  
Long Chain Fatty Acids ◽  
Fatty Acid Elongase ◽  
Fatty Acylation ◽  
Dynamics Simulations ◽  
Long Chain ◽  
Chain Fatty Acids

In this work we investigate the mechanisms by which very long chain fatty acids (VLCFA) contribute to membrane permeabilization during necroptosis, a form of highly regulated necrotic cell death. We show that inactivating fatty acid elongase ELOVL7 prevents VLCFA accumulation and necroptotic cell death, while it's overexpression causes membrane permeabilization. We show that VLCFA can directly permeabilize lipid bilayers and investigate the basis of these effects by molecular dynamics simulations. Finally, we show that VLCFA can be used as substrates for protein fatty acylation during necroptosis, suggesting another potential mechanism by which VLCFA may mediate membrane permeabilization.

Membrane Disruption by Very Long Chain Fatty Acids During Necroptosis

2019 ◽  
Author(s):  
Laura Parisi ◽  
Shahin Sowlati-Hashjin ◽  
Ilyas Berhane ◽  
Kevin Carter ◽  
Jonathan Lovell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Lipid Bilayers ◽  
Membrane Permeabilization ◽  
Long Chain Fatty Acids ◽  
Fatty Acid Elongase ◽  
Fatty Acylation ◽  
Dynamics Simulations ◽  
Long Chain ◽  
Chain Fatty Acids

In this work we investigate the mechanisms by which very long chain fatty acids (VLCFA) contribute to membrane permeabilization during necroptosis, a form of highly regulated necrotic cell death. We show that inactivating fatty acid elongase ELOVL7 prevents VLCFA accumulation and necroptotic cell death, while it's overexpression causes membrane permeabilization. We show that VLCFA can directly permeabilize lipid bilayers and investigate the basis of these effects by molecular dynamics simulations. Finally, we show that VLCFA can be used as substrates for protein fatty acylation during necroptosis, suggesting another potential mechanism by which VLCFA may mediate membrane permeabilization.

Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids

2014 ◽  
Vol 31 (5) ◽  
pp. 453-475 ◽  
Author(s):  
Mohamad Hafizi Abu Bakar ◽  
Cheng Kian Kai ◽  
Wan Najihah Wan Hassan ◽  
Mohamad Roji Sarmidi ◽  
Harisun Yaakob ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E)

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Amira Zarrouk ◽  
Anne Vejux ◽  
Thomas Nury ◽  
Hammam I. El Hajj ◽  
Madouda Haddad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Counting ◽  
Long Chain Fatty Acids ◽  
Superoxide Anion Production ◽  
Mitochondrial Dysfunctions ◽  
Whole Cells ◽  
Potential Risk Factors ◽  
Long Chain ◽  
Chain Fatty Acids

In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomalβ-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with DiOC6(3). A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions.

scholarly journals Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model

2020 ◽  
Vol 21 (2) ◽  
pp. 641 ◽  
Author(s):  
Thomas Nury ◽  
Margaux Doria ◽  
Gérard Lizard ◽  
Anne Vejux
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Western Blot Assay ◽  
Cytotoxic Effects ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

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.

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