Free radical release in C6 glial cells enriched in hexacosanoic acid: implication for X-linked adrenoleukodystrophy pathogenesis.
Free radicals have been implicated in the etiopathology of some neurological and demyelinating diseases. To evaluate their involvement in the cerebral form of X-linked adrenoleukodystrophy (cerALD) disorder, characterised by very long chain fatty acid (VLCFA) accumulation, we utilised an in vitro model using rat C6 glial cells, enriched in hexacosenoic acid (C26:0, HA). Modified cells were incubated in presence of oxidative stressors, such as bacterial endotoxin lipopolisaccharides (LPS) and human oxidised low-density lipoprotein (ox-LDL), and the production of proinflammatory cytokines, nitrite, nitrate and superoxide was determined in the supernatants. The results show that modified cells produce higher amounts of nitric oxide (NO) products and superoxide compared to native C6 cells, supporting the role of free radicals as important pathophysiological modulator of the neuroinflammatory response in ALD. This hypothesis suggests that the cerebral damage in ALD could be due to intracellular signalling activated by interaction of exogenous factors with the particular membrane fatty acid composition.
Di Biase
Antonella
A
Department of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. dibiase@iss.it
Di Benedetto
Rita
R
Fiorentini
Carla
C
Travaglione
Sara
S
Salvati
Serafina
S
Attorri
Lucilla
L
Pietraforte
Donatella
D
D000326:Adrenoleukodystrophy / Q000209:etiology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005227:Fatty Acids / Q000008:administration & dosage*; D005609:Free Radicals; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats
D016207:Cytokines; D005227:Fatty Acids; D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; C017364:hexacosanoic acid