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Pharmaceutics 2011, 3(4), 782-792; doi:10.3390/pharmaceutics3040782

Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells

1, 2, 1, 3, 1,3, 2 and 1,*
Received: 22 September 2011 / Revised: 11 October 2011 / Accepted: 20 October 2011 / Published: 27 October 2011
(This article belongs to the Special Issue Transporter-Mediated Drug Interactions)
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Abstract: P-glycoprotein (P-gp) is an ATP-dependent transporter localized at the apical membrane of the kidney proximal tubules, which plays a role in the efflux of cationic and amphipathic endogenous waste products and xenobiotics, such as drugs, into urine. Studies in mice deficient in P-gp showed generalized proximal tubular dysfunction similar to the phenotype of patients with cystinosis, an autosomal recessive disorder caused by mutations in the lysosomal cystine transporter cystinosin. Renal disease in cystinosis is characterized by generalized dysfunction of the apical proximal tubular influx transporters (so-called renal Fanconi syndrome) developing during infancy and gradually progressing towards end-stage renal disease before the 10th birthday in the majority of patients that are not treated with the cystine-depleting drug cysteamine. Here, we investigated whether the proximal tubular efflux transporter P-gp is affected in cystinosis and whether this might contribute to the development of renal Fanconi syndrome. We used conditionally immortalized (ci) proximal tubular epithelial cells (ciPTEC) derived from cystinotic patients and healthy volunteers. P-gp-mediated transport was measured by using the P-gp substrate calcein-AM in the presence and absence of the P-gp-inhibitor PSC833. P-gp activity was normal in cystinotic cells as compared to controls. Additionally, the effect of cysteamine on P-gp transport activity and phosphate uptake was determined; demonstrating increased P-gp activity in cystinotic cells, and further decrease of proximal tubular phosphate uptake. This observation is compatible with the persistence of renal Fanconi syndrome in vivo under cysteamine therapy. In summary, P-gp expression and activity are normal in cystinotic ciPTEC, indicating that P-gp dysfunction is not involved in the pathogenesis of cystinosis.
Keywords: cystinosis; P-glycoprotein; renal proximal tubular cell; cysteamine cystinosis; P-glycoprotein; renal proximal tubular cell; cysteamine
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Peeters, K.; Wilmer, M.J.; Schoeber, J.P.; Reijnders, D.; Heuvel, L.P.; Masereeuw, R.; Levtchenko, E. Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells. Pharmaceutics 2011, 3, 782-792.

AMA Style

Peeters K, Wilmer MJ, Schoeber JP, Reijnders D, Heuvel LP, Masereeuw R, Levtchenko E. Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells. Pharmaceutics. 2011; 3(4):782-792.

Chicago/Turabian Style

Peeters, Karen; Wilmer, Martijn J.; Schoeber, Joost P.; Reijnders, Dorien; Heuvel, Lambertus P. van den; Masereeuw, Rosalinde; Levtchenko, Elena. 2011. "Role of P-Glycoprotein Expression and Function in Cystinotic Renal Proximal Tubular Cells." Pharmaceutics 3, no. 4: 782-792.

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