Effect of nitric oxide on lymphocytes from sporadic amyotrophic lateral sclerosis patients: toxic or protective role?
Markers of oxidative and nitrosative stress have been found in spinal cord, cortex, cerebrospinal fluid and plasma of patients affected by amyotrophic lateral sclerosis (ALS), a fatal disorder characterised by progressive motor neuron degeneration. In this study, we investigated the effect of the NO-releasing agent, diethylamine NONOate (NONO), on lymphocytes from patients affected by the sporadic form of ALS (SALS) and controls by flow cytometry. In the same experimental conditions we investigated the expression of the antioxidant proteins, Bcl-2 and SOD1. Incubation with NONO induced cell damage in control lymphocytes but did not further damage the already affected untreated SALS lymphocytes. The incubation with NONO induced a time-dependent decrease of Bcl-2 and SOD1 in control lymphocytes. Surprisingly, in SALS lymphocytes the NONO treatment increased the expression of these proteins, which in basal conditions was depressed compared to control lymphocytes.
Cereda
C
C
Laboratory of Experimental Neurobiology, I.R.C.C.S. Foundation C. Mondino Institute of Neurology, Centro Ricerche, Via Mondino 1, I-27100 Pavia, Italy. cristina.cereda@mondino.it
Cova
E
E
Di Poto
C
C
Galli
A
A
Mazzini
G
G
Corato
M
M
Ceroni
M
M
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000704:Analysis of Variance; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D006801:Humans; D006834:Hydrazines / Q000378:metabolism* / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors
D006834:Hydrazines; D020030:Nitric Oxide Donors; D019253:Proto-Oncogene Proteins c-bcl-2; C000606290:SOD1 protein, human; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1