Cystine loading induces Fanconi's syndrome in rats: In vivo and vesicle studies

A. Ben-Nun, N. Bashan, R. Potashnik, R. Cohen-Luria, A. Moran

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


To better understand the link between lysosomal cystine accumulation and the renal impairment seen in cystinosis, we have studied the effect of cystine loading in vivo, on renal function of rats, and in brush-border membrane vesicles (BBMV) prepared from the kidney cortex of the treated rats. Intraperitoneal injection of cystine dimethyl ester (CDME) (400 μmol, twice a day, for 5 days) led to an increased urine volume and excretion of glucose, phosphate, and protein. Kinetic analysis of α-methylglucoside initial flux in BBMV showed reduction in maximal transport capacity (Vmax, from 10.1 ± 1.3 to 8.5 ± 0.7 nmol·min-1·mg protein-1; P < 0.01) with no change in Michaelis constant (Km, 4.80 ± 0.08 and 4.90 ± 0.05 mM). The number of phlorizin binding sites declined (from 6.5 ± 0.7 to 4.1 ± 0.4 pmol/mg protein; P < 0.01) with no significant change in the affinity for phlorizin (0.64 ± 0.08 and 0.59 ± 0.06 μM). In the cortex homogenate, cystine concentration, which was undetectable in controls, increased to 0.97 ± 0.09 nmol 1/2 cystine/mg protein. Two hours after CDME administration, ATP content declined to ∼50% of control values. This decline was transient, and ATP content was recovered to control values 5 h after CDME administration. The treatment did not affect ouabain-sensitive adenosinetriphosphatase activity (40.0 ± 3.9 and 38.6 ± 4.7 nmol Pi·mg protein-1·min-1) or the number and affinity of ouabain binding sites (Bmax = 1.48 ± 0.25 and 1.44 ± 0.18 pmol/mg, and Kd = 0.68 ± 0.09 and 0.72 ± 0.12 μM, respectively). We postulate that the reduction in ATP content and sodium-coupled glucose absorption may, at least partially, be the basis for the Fanconi's syndrome seen in the CDME-treated rats and is probably one of the mechanisms for the proximal tubular impairment seen in cystinotic patients.

Original languageEnglish
Pages (from-to)F839-F844
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number6 34-6
StatePublished - 1 Jan 1993


  • Brush-border membrane vesicles
  • Cystine dimethyl ester
  • Cystinosis
  • Phlorizin binding
  • Sodium-coupled transport
  • Sodium-potassium-adenosinetriphosphatase

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Cystine loading induces Fanconi's syndrome in rats: In vivo and vesicle studies'. Together they form a unique fingerprint.

Cite this