Article (Scientific journals)
Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-alpha on oligodendrocytes and astrocytes
Baarine, Mauhamad; Ragot, Kevin; Athias, Anne et al.
2012In NeuroToxicology, 33(2), p. 212-28
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Keywords :
very long chain fatty acids; TNF-alpha; cell death; mitochondria; lysosome; peroxisome; glial cells; oligodendrocytes; glioma cells
Abstract :
[en] X-linked adrenoleukodystrophy (X-ALD) is characterized by ABCD1 deficiency. This disease is associated with elevated concentrations of very long chain fatty acids (C24:0 and C26:0) in the plasma and tissues of patients. Under its severe form, brain demyelination and inflammation are observed. Therefore, we determined the effects of C24:0 and C26:0 on glial cells:oligodendrocytes, which synthesize myelin, and astrocytes, which participate in immune response. So, 158N murine oligodendrocytes, rat C6 glioma cells, rat primary cultures of neuronal–glial cells, and of oligodendrocytes were treated for various periods of time in the absence or presence of C24:0 and C26:0 used at plasmatic concentrations found in X-ALD patients (1–5 μM) and higher (10, 20, 40 μM). To evaluate the importance of extrinsic and intrinsic factors, the part taken by TNF-α and reduced Abcd1 level was studied. Whatever the cells considered, no effects on cell growth and/or viability were detected at 1–5 μM, more or less pronounced effects were identified at 10 μM, and an induction of cell death with increased permeability to propidium iodide and loss of transmembrane mitochondrial potential was observed at 20–40 μM. On 158N, cell death was characterized by (i) an increased superoxide anion production at the mitochondrial level; (ii) the presence of vacuoles of different sizes and shapes; a destabilization of lysosomal membrane and a cytoplasmic redistribution of lysosomes; (iii) a modulation of Abcd3/PMP70 and Acox-1 protein expression, and a decrease in catalase activity at the peroxisomal level. When TNF-α was combined with C24:0 or C26:0 and used on 158N cells, C6 cells, and on 158N cells after siRNA mediated knockdown of Abcd1, no or slight potentiation was revealed. Thus, on the different cell models used, an induction of cell death with marked cellular dysfunctions at the mitochondrial, lysosomal, and peroxisomal levels were found with C24:0 and C26:0 at 20 μM and higher. However, in our experimental conditions, plasmatic concentrations of these fatty acids were unable to induce cell death, and organelle dysfunctions on oligodendrocytes and astrocytes, and additional intrinsic and environmental factors, such as reduced Abcd1 level and/or TNF-α, were ineffective to potentiate their side effects.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Baarine, Mauhamad;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Ragot, Kevin;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Athias, Anne;  INSERM IFR100 ‘Santé – STIC’ > Plateau Technique de Lipidomique, Dijon, France
Nury, Thomas;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Kattan, Zilal;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Genin, Emmanuelle ;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Andreoletti, Pierre;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Ménétrier, Franck;  INRA, UMR Centre des Sciences du Goût et de l’Alimentation (CSGA) > Développement et Dynamique des Préférences et du Comportement Alimentaire, Dijon, France
Riedinger, Jean-Marc;  Centre de Lutte Contre le Cancer GF Leclerc > Laboratoire de Biologie Médicale, Dijon, France
Bardou, Marc;  INSERM CIC-P 803/CHU de Dijon, Dijon, France
Lizard, Gérard;  Centre de Recherche INSERM 866, Université de Bourgogne > ‘Lipides, Nutrition, Cancer’ > Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique, Dijon, France
Language :
English
Title :
Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-alpha on oligodendrocytes and astrocytes
Publication date :
March 2012
Journal title :
NeuroToxicology
ISSN :
0161-813X
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
33(2)
Pages :
212-28
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 March 2012

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