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Regulation of TauT by cisplatin in LLC-PK1 renal cells

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Abstract

Cisplatin is a commonly used chemotherapeutic agent that has a major limitation because of its nephrotoxicity. Since cisplatin-induced renal injury is mainly confined to the S3 segment of renal proximal tubules—the primary site for renal adaptive regulation of TauT—we hypothesize that TauT functions as an anti-apoptotic gene and plays a role in protecting renal cells from drug-induced nephrotoxicity. In the present study we demonstrated that expression of TauT was significantly reduced by cisplatin (50 μM) in LLC-PK1 cells. Down-regulation of TauT by cisplatin occurs at the transcriptional level in a dose-dependent manner, as demonstrated through a reporter gene driven by the TauT promoter. It appears that cisplatin down-regulates TauT expression, at least in part, through the p53-dependent pathway, since cisplatin induces the p53 expression, which, in turn, represses TauT. Cisplatin induces apoptosis of LLC-PK1 cells in a dose-dependent manner. However, forced over-expression of TauT by stable transfection of a taurine transporter cDNA (pNCT) in LLC-PK1 cells was able to attenuate cisplatin-induced down-regulation of taurine uptake by LLC-PK1 cells and protect renal tubular cells from apoptosis. The mechanism by which TauT serves as an anti-apoptotic gene in cisplatin-induced renal injury remains to be determined, but could relate to taurine-dependent cell volume regulation.

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Acknowledgements

The authors wish to thank Andrea Patters for insightful comments and suggestions. This work was supported by grants from the National Kidney Foundation and Le Bonheur Chair of Excellence in Pediatrics.

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Authors and Affiliations

  1. Department of Pediatrics, University of Tennessee, Memphis, 50 N. Dunlap, Memphis, TN 38103, USA

    X. Han

  2. Department of Pediatrics, University of Tennessee Health Science Center, and the Children’s Foundation Research Center at Le Bonheur Children’s Medical Center, Memphis, Tennessee, USA

    X. Han & R. W. Chesney

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  1. X. Han
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  2. R. W. Chesney
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Correspondence to X. Han.

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Han, X., Chesney, R.W. Regulation of TauT by cisplatin in LLC-PK1 renal cells. Pediatr Nephrol 20, 1067–1072 (2005). https://doi.org/10.1007/s00467-005-1887-8

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  • DOI: https://doi.org/10.1007/s00467-005-1887-8

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