Glutathione in blood of patients with Friedreich's ataxia

F. Piemonte, A. Pastore, G. Tozzi, D. Tagliacozzi, F. M. Santorelli, R. Carrozzo, C. Casali, M. Damiano, G. Federici, E. Bertini

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

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. Materials and 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.

Original languageEnglish
Pages (from-to)1007-1011
Number of pages5
JournalEuropean Journal of Clinical Investigation
Volume31
Issue number11
DOIs
Publication statusPublished - 2001

Fingerprint

Friedreich Ataxia
Glutathione
Blood
Hemoglobins
Neurodegenerative diseases
Oxidative stress
Metabolism
Neurodegenerative Diseases
Oxidative Stress
Electrospray ionization
Electrospray Ionization Mass Spectrometry
Mitochondrial Proteins
Liquid chromatography
Reverse-Phase Chromatography
Cytotoxicity
Free Radicals
Mass spectrometry
Healthy Volunteers
Homeostasis
Iron

Keywords

  • Friedreich's ataxia
  • Glutathione
  • Glutathionyl-haemoglobin
  • Neurodegenerative disease
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Glutathione in blood of patients with Friedreich's ataxia. / Piemonte, F.; Pastore, A.; Tozzi, G.; Tagliacozzi, D.; Santorelli, F. M.; Carrozzo, R.; Casali, C.; Damiano, M.; Federici, G.; Bertini, E.

In: European Journal of Clinical Investigation, Vol. 31, No. 11, 2001, p. 1007-1011.

Research output: Contribution to journalArticle

Piemonte, F. ; Pastore, A. ; Tozzi, G. ; Tagliacozzi, D. ; Santorelli, F. M. ; Carrozzo, R. ; Casali, C. ; Damiano, M. ; Federici, G. ; Bertini, E. / Glutathione in blood of patients with Friedreich's ataxia. In: European Journal of Clinical Investigation. 2001 ; Vol. 31, No. 11. pp. 1007-1011.
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T1 - Glutathione in blood of patients with Friedreich's ataxia

AU - Piemonte, F.

AU - Pastore, A.

AU - Tozzi, G.

AU - Tagliacozzi, D.

AU - Santorelli, F. M.

AU - Carrozzo, R.

AU - Casali, C.

AU - Damiano, M.

AU - Federici, G.

AU - Bertini, E.

PY - 2001

Y1 - 2001

N2 - 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. Materials and 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.

AB - 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. Materials and 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.

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