Glutathione precursors replenish decreased glutathione pool in cystinotic cell lines.
Cystinosis is an inherited disorder due to mutations in the CTNS gene which encodes cystinosin, a lysosomal transmembrane protein involved in cystine export to the cytosol. Both accumulation of cystine in the lysosome and decreased cystine in the cytosol may participate in the pathogenic mechanism underlying the disease. We observed that cystinotic cell lines have moderate decrease of glutathione content during exponential growth phase. This resulted in increased solicitation of oxidative defences of the cell denoted by concurrent superoxide dismutase induction, although without major oxidative insult under our experimental conditions. Finally, decreased glutathione content in cystinotic cell lines could be counterbalanced by a series of exogenous precursors of cysteine, denoting that lysosomal cystine export is a natural source of cellular cysteine in the studied cell lines.
Chol
Marie
M
INSERM U574, Néphropathies Héréditaires et Rein en Développement, Hôpital Necker-Enfants Malades, rue de Sèvres, 75015 Paris, France.
Nevo
Nathalie
N
Cherqui
Stéphanie
S
Antignac
Corinne
C
Rustin
Pierre
P
D000293:Adolescent; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002460:Cell Line; D002648:Child; D003553:Cystine / Q000378:metabolism; D003554:Cystinosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009154:Mutation; D010084:Oxidation-Reduction; D011498:Protein Precursors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D003553:Cystine; D013482:Superoxide Dismutase; D005978:Glutathione