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Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells
- Source :
- Biochimica et Biophysica Acta. Molecular Basis of Disease, 1812, 643-51, Biochimica et Biophysica Acta. Molecular Basis of Disease, 1812(6), 643-651. Elsevier, Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, Wilmer, M J, Kluijtmans, L A J, van der Velden, T J, Willems, P H, Scheffer, P G, Masereeuw, R, Monnens, L A, van den Heuvel, L P & Levtchenko, E N 2011, ' Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells ', Biochimica et Biophysica Acta. Molecular Basis of Disease, vol. 1812, no. 6, pp. 643-651 . https://doi.org/10.1016/j.bbadis.2011.02.010, Biochimica et Biophysica Acta. Molecular Basis of Disease, 1812, 6, pp. 643-51, Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease; Vol 1812
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Contains fulltext : 95780.pdf (Publisher’s version ) (Closed access) 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 newly 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 less negative glutathione redox status and decreased 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.
- Subjects :
- Male
Cystinosis
030232 urology & nephrology
medicine.disease_cause
Kidney Tubules, Proximal
chemistry.chemical_compound
0302 clinical medicine
Adenosine Triphosphate
Child
Cells, Cultured
Renal disorder [IGMD 9]
0303 health sciences
Mitochondrial medicine Energy and redox metabolism [IGMD 8]
Functional imaging [IGMD 1]
Glutathione
3. Good health
Renal disorder Membrane transport and intracellular motility [IGMD 9]
ATP production
Redox status
Cystinosin
Child, Preschool
Molecular Medicine
Female
Oxidation-Reduction
medicine.medical_specialty
Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3]
Energy and redox metabolism [NCMLS 4]
Adolescent
Cysteamine
Cystine
Renal disorder Energy and redox metabolism [IGMD 9]
End stage renal disease
Genomic disorders and inherited multi-system disorders [IGMD 3]
03 medical and health sciences
Nephropathic Cystinosis
Internal medicine
medicine
Humans
Molecular Biology
030304 developmental biology
Cell Proliferation
Infant
Epithelial Cells
medicine.disease
Membrane transport and intracellular motility Renal disorder [NCMLS 5]
Endocrinology
chemistry
Oxidative stress
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1812
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Accession number :
- edsair.doi.dedup.....0affcf2f136725a5944fb82906ded065
- Full Text :
- https://doi.org/10.1016/j.bbadis.2011.02.010