Modified expression of Bcl-2 and SOD1 proteins in lymphocytes from sporadic ALS patients.
Markers of oxidative stress have been found in spinal cord, cortex, cerebrospinal fluid, and plasma of SALS patients. Mitochondrial and calcium metabolism dysfunction were also found in peripheral lymphocytes from SALS patients. In this study, we demonstrate that lymphocytes from SALS patients are more prone to undergo alteration of cell membrane integrity both in basal conditions and following oxidative stress induced by H2O2 treatment. The expression of the antioxidant proteins, Bcl-2, SOD1 and catalase in basal conditions, was significantly lower in lymphocytes from SALS patients than in lymphocytes from age and sex matched controls. Exposure to H2O2 induced a time-dependent decrease of Bcl-2 and SOD1 in control lymphocytes. Conversely, the levels of these proteins remained unchanged in SALS lymphocytes even after 18 h stress. Catalase expression was not significantly modified by oxidative stress. Our results demonstrate that two factors involved in the genesis and/or progression of the familial form of the disease with SOD1 mutation are altered also in the sporadic form of ALS and suggest that the oxidative stress protection pathway is deregulated in lymphocytes from ALS patients.
Laboratory of Experimental Neurobiology, IRCCS, Foundation C. Mondino Institute of Neurology, via Mondino, 2, 27100 Pavia, Italy. emanuela.cova@mondino.it
Emanuela
E
Cova
Cristina
C
Cereda
Alberto
A
Galli
Daniela
D
Curti
Chiara
C
Finotti
Cristina
C
Di Poto
Manuel
M
Corato
Giuliano
G
Mazzini
Mauro
M
Ceroni
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2; C000606290:SOD1 protein, human; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1