Abstract
Background: X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition. Methods: Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays. Results: A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls. Conclusion: Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease.
| Original language | English |
|---|---|
| Pages (from-to) | 366-370 |
| Number of pages | 5 |
| Journal | Molecular Genetics and Metabolism |
| Volume | 109 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Aug 2013 |
Fingerprint
Keywords
- Glutathione
- Oxidative stress
- Redox markers
- X-linked adrenoleukodystrophy (X-ALD)
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
- Endocrinology
- Endocrinology, Diabetes and Metabolism
- Medicine(all)
Cite this
Glutathione imbalance in patients with X-linked adrenoleukodystrophy. / Petrillo, Sara; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Aiello, Chiara; Pujol, Aurora; Cappa, Marco; Bertini, Enrico.
In: Molecular Genetics and Metabolism, Vol. 109, No. 4, 08.2013, p. 366-370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glutathione imbalance in patients with X-linked adrenoleukodystrophy
AU - Petrillo, Sara
AU - Piemonte, Fiorella
AU - Pastore, Anna
AU - Tozzi, Giulia
AU - Aiello, Chiara
AU - Pujol, Aurora
AU - Cappa, Marco
AU - Bertini, Enrico
PY - 2013/8
Y1 - 2013/8
N2 - Background: X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition. Methods: Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays. Results: A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls. Conclusion: Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease.
AB - Background: X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition. Methods: Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays. Results: A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls. Conclusion: Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease.
KW - Glutathione
KW - Oxidative stress
KW - Redox markers
KW - X-linked adrenoleukodystrophy (X-ALD)
UR - http://www.scopus.com/inward/record.url?scp=84880831771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880831771&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2013.05.009
DO - 10.1016/j.ymgme.2013.05.009
M3 - Article
C2 - 23768953
AN - SCOPUS:84880831771
VL - 109
SP - 366
EP - 370
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
SN - 1096-7192
IS - 4
ER -