Effects of L-mono methyl-arginine, N-acetyl-cysteine and diphenyleniodonium on free radical release in C6 glial cells enriched in hexacosenoic acid.
Previously, we have shown that C6 glial cells enriched in hexacosenoic acid (HA) incubated with oxidative stressors released higher amounts of nitric oxide (NO) products and superoxide (O2(-)), compared to native C6 cells. In the present study, we examined the effects of pretreatment with some of free radical release inhibitors. The aim was to determine the origin of the enhanced generation of NO and superoxide, and to test the possibility of preventing it. Pre-treatment with L-mono-methyl-arginine and N-acetyl-cysteine in oxidized low-density lipoprotein (ox-LDL) exposed HA cells, inhibited not only nitrite but also superoxide production suggesting that O2(-) anion could partially derive from inducible NO synthase. We also observed that ox-LDL treatment of HA cells reduced the intracellular glutathione levels and activated extracellular signal-related kinases. Since this signalling is related to neurotoxic effect, our data substantiate the role of the free radicals in X-linked adrenoleukodystrophy pathogenesis, as HA cells have been used as an in vitro model for this disease.
Di Biase
Antonella
A
Food Science, Nutrition and Health Division, Instituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy. dibiase@iss.it
Di Benedetto
Rita
R
Salvati
Serafina
S
Attorri
Lucilla
L
Leonardi
Fabiana
F
Pietraforte
Donatella
D
D000111:Acetylcysteine / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009861:Onium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000633:toxicity*
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D016166:Free Radical Scavengers; D005609:Free Radicals; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D009861:Onium Compounds; D013481:Superoxides; C040938:1-hexacosenoic acid; D019323:omega-N-Methylarginine; C007517:diphenyleneiodonium; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D000111:Acetylcysteine