Glutathione imbalance in patients with X-linked adrenoleukodystrophy
| Autor: | Anna Pastore, Fiorella Piemonte, Chiara Aiello, Aurora Pujol, Giulia Tozzi, Enrico Bertini, Sara Petrillo, Marco Cappa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Antioxidant Adolescent Free Radicals Endocrinology Diabetes and Metabolism medicine.medical_treatment Glutathione reductase GPX4 medicine.disease_cause ATP Binding Cassette Transporter Subfamily D Member 1 Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Genetics medicine Humans Lymphocytes Sulfhydryl Compounds Adrenoleukodystrophy Child Molecular Biology 030304 developmental biology Whole blood 0303 health sciences Glutathione Disulfide X-linked adrenoleukodystrophy (X-ALD) Glutathione Middle Aged medicine.disease 3. Good health Redox markers Oxidative Stress chemistry Child Preschool Mutation Glutathione disulfide ATP-Binding Cassette Transporters Female 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Molecular Genetics and Metabolism; Vol 109 Molecular Genetics and Metabolism |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2013.05.009 |
| Popis: | 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. Highlights • All glutathione forms are abnormal in blood of X-ALD patients. • Abnormal oxidative stress in X-ALD is confirmed by decrease of thiols in plasma. • Abnormal oxidative stress in X-ALD is confirmed by increased carbonyls in plasma. • Glutathione may be considered a redox hallmark/potential biomarker in X-ALD. |
| Databáze: | OpenAIRE |
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