title: Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.
abstract: Recent findings indicate that nitric oxide (NO*) over-production might be an important factor in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higher concentrations of uric acid and thiol group-containing molecules (R-SH groups) in the cerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, together with a slightly increased free iron concentration found in the CSF, favour conditions necessary for the formation of the dinitrosyl iron complex, capable of NO* bio-transformation. Thus, we performed ex vivo saturation of CSF (from both SALS patients and controls) with NO*. A decrease in the level of R-SH was found. This was more pronounced in the CSF from SALS patients. In the CSF from SALS patients the production of nitrite and hydroxylamine was greater than that observed in the CSF from controls. Moreover, we also found increased Cu,Zn-SOD activity in the CSF from SALS patients (when compared to control subjects) but no activity corresponding to Mn-SOD in any CSF samples. As Cu,Zn-SOD can react with nitroxyl forming NO*, the conditions for a closed, but continuous, loop of NO* biotransformation are present in the CSF of ALS patients.
authors.affiliation: Department of Physiology, Institute for Biological Research Sinisa Stanković, Belgrade, Serbia and Montenegro.
authors.forename: Aleksandra Nikolić
authors.initials: AN
authors.lastname: Kokić
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stević
authors.forename: Srdjan
authors.initials: S
authors.lastname: Stojanović
authors.forename: Dusko P
authors.initials: DP
authors.lastname: Blagojević
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlović
authors.forename: Vesna
authors.initials: V
authors.lastname: Niketić
authors.forename: Slobodan
authors.initials: S
authors.lastname: Apostolski
authors.forename: Mihajlo B
authors.initials: MB
authors.lastname: Spasić
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D019811:Hydroxylamine / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D009573:Nitrites / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D009573:Nitrites; D009589:Nitrogen Oxides; D019811:Hydroxylamine; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D007501:Iron; D013482:Superoxide Dismutase