Document Detail

Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells.
MedLine Citation:
PMID:  21371554     Owner:  NLM     Status:  Publisher    
Recent evidence implies that impaired metabolism of glutathione has a role in the pathogenesis of nephropathic cystinosis. This recessive inherited disorder is characterized by lysosomal cystine accumulation and results in renal Fanconi syndrome progressing to end stage renal disease in the majority of patients. The most common treatment involves intracellular cystine depletion by cysteamine, delaying the development of end stage renal disease by a yet elusive mechanism. However, cystine depletion does not arrest the disease nor cures Fanconi syndrome in patients, indicating involvement of other yet unknown pathologic pathways. Using a new developed proximal tubular epithelial cell model from cystinotic patients, we investigate the effect of cystine accumulation and cysteamine on both glutathione and ATP metabolism. In addition to the expected increase in cystine and defective sodium-dependent phosphate reabsorption, we observed a decrease in glutathione redox status and intracellular ATP levels. No differences between control and cystinosis cell lines were observed with respect to protein turnover, albumin uptake, cytosolic and mitochondrial ATP production, total glutathione levels, protein oxidation and lipid peroxidation. Cysteamine treatment increased total glutathione in both control and cystinotic cells and normalized cystine levels and glutathione redox status in cystinotic cells. However, cysteamine did not improve decreased sodium-dependent phosphate uptake. Our data implicate that cysteamine increases total glutathione and restores glutathione redox status in cystinosis, which is a positive side-effect of this agent next to cystine depletion. This beneficial effect points to a potential role of cysteamine as anti-oxidant for other renal disorders associated with enhanced oxidative stress.
Martijn J Wilmer; Leo A J Kluijtmans; Thea J van der Velden; Peter H Willems; Peter G Scheffer; Rosalinde Masereeuw; Leo A Monnens; Lambertus P van den Heuvel; Elena N Levtchenko
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-28
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  -     ISSN:  0006-3002     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier B.V.
Laboratory of Genetic Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, The Netherlands; Department of Pediatrics, University Hospital, Leuven, Belgium; Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, The Netherlands.
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