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).
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 peroxisomal β-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 (Δψ(m)) with DiOC(6)(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.
Equipe Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (EA 7270), Faculté des Sciences, Université de Bourgogne, 21000 Dijon, France.
Amira
A
Zarrouk
Anne
A
Vejux
Thomas
T
Nury
Hammam I
HI
El Hajj
Madouda
M
Haddad
Mustapha
M
Cherkaoui-Malki
Jean-Marc
JM
Riedinger
Mohamed
M
Hammami
Gérard
G
Lizard
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D046912:Multiprotein Complexes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D021122:Protein Subunits / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D005227:Fatty Acids; D046912:Multiprotein Complexes; D021122:Protein Subunits; D013481:Superoxides