Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

Recent findings indicate that nitric oxide (NOcenter dot) 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 NOcenter dot bio-transformation. Thus, we performed ex vivo saturation of CSF ( from both SALS patients and controls) with NOcenter dot. 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 NOcenter dot, the conditions for a closed, but continuous, loop of NOcenter dot biotransformation are present in the CSF of ALS patients.