Cystine dimethyl ester reduces the forces driving sodium-dependent transport in LLC-PK1 cells
| Autor: | Arie Moran, A. Ben-Nun, R. Cohen-Luria, N. Bashan, R. Potashnik |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Sodium-Hydrogen Exchangers
Physiology Sodium-Potassium-Exchanging ATPase Sodium Antiporter Cystine chemistry.chemical_element Kidney Epithelium Cell Line chemistry.chemical_compound Animals Na+/K+-ATPase Biological Transport Epithelial Cells Intracellular Membranes Cell Biology Membrane transport Rubidium Sodium–hydrogen antiporter Glucose Biochemistry chemistry Potassium Biophysics Carrier Proteins Intracellular |
| Zdroj: | American Journal of Physiology-Cell Physiology. 263:C516-C520 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1992.263.2.c516 |
| Popis: | Cystinosis is an inherited metabolic disease characterized by accumulation of lysosomal cystine and renal impairment. In an attempt to better understand the link between cystine accumulation and renal functions, we studied the effects of cystine loading on the Na(+)-H+ antiporter and the sodium pump in renal epithelial cells (LLC-PK1) in culture. Incubation of LLC-PK1 with 1 mM cystine dimethyl ester (CDME) for 48 h caused lysosomal cystine loading and reduced by 22 +/- 2% the maximal velocity of sodium-hydrogen antiport with no significant change in the affinity of sodium for the transporter. Rubidium influx decreased to 46 +/- 5% of control. Ouabain binding experiments revealed a 10% reduction in the number of Na(+)-K(+)-ATPase units in the intact cells. Na(+)-K(+)-ATPase activity in the particulate fraction of the cells homogenate declined to 50 +/- 7.5% of controls. No significant change was observed in the activity of ouabain-insensitive phosphatases. The intracellular concentration of sodium increased from 20.6 +/- 3.7 to 64.8 +/- 10 mM, and potassium concentration decreased from 103 +/- 6 to 80 +/- 13 mM. In addition to the observed reduction in the sodium gradient and in agreement with the reduction in the intracellular potassium concentration, the membrane potential changed from -80.8 +/- 7.5 to -69.9 +/- 7.0 mV. The results suggest that intracellular accumulation of cystine is associated with reduction in the number and the activity of membrane transporters. The consequence of the changes in the activity of Na(+)-K(+)-ATPase is a reduction in the electrochemical forces that drive transport in the renal cells tested.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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