Glutathione in blood of patients with Friedreich's ataxia.
BACKGROUND
Oxidative stress and mitochondrial dysfunction have long been considered to play a role in Friedreich's ataxia, a neurodegenerative disease due to a GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Since glutathione is an important antioxidant whose role has been recently proposed in the pathogenesis of some neurodegenerative diseases, we investigated glutathione metabolism in the blood of 14 patients with Friedreich's ataxia by measuring total, free and protein-bound glutathione concentrations.


METHODS
Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia (nine males, five females) and 20 age-matched healthy controls (10 males, 10 females). Total and free glutathione concentrations were determined by reverse-phase liquid chromatography with fluorescence detection; the glutathionyl-haemoglobin separation from healthy and pathological subjects was obtained by electrospray ionization-mass spectrometry.


RESULTS
We consistently found a reduction of free glutathione levels (0.55 +/- 0.06 nmol mg(-1) haemoglobin, vs. 8.4 +/- 1.79 nmol mg(-1) haemoglobin, P < 0.001) in the blood of patients with Friedreich's ataxia, a total glutathione concentration comparable to the controls (15 +/- 2.6 nmol mg(-1) haemoglobin, vs. 15.4 +/- 1.4 nmol mg(-1) haemoglobin), and a significant increase of glutathione bound to haemoglobin (15 +/- 1.5 vs. 8 +/- 1.8%, P < 0.05) in erythrocytes.


CONCLUSIONS
Our findings give evidence of an impairment in vivo of glutathione homeostasis in Friedreich's ataxia, suggesting a relevant role of free radical cytotoxicity in the pathophysiology of the disease; this study may also prove useful in the search for an oxidative stress marker in neurodegeneration.
Piemonte
F
F
Molecular Medicine Laboratory, Bambino Gesù Children's Hospital, P.za S. Onofrio, 4-00165 Rome, Italy. Fiorellait@hotmail.com
Pastore
A
A
Tozzi
G
G
Tagliacozzi
D
D
Santorelli
F M
FM
Carrozzo
R
R
Casali
C
C
Damiano
M
M
Federici
G
G
Bertini
E
E
D000293:Adolescent; D000328:Adult; D002648:Child; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood* / Q000503:physiopathology; D005978:Glutathione / Q000097:blood*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D021241:Spectrometry, Mass, Electrospray Ionization
D006454:Hemoglobins; C404464:glutathionyl hemoglobin; D005978:Glutathione