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MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells

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Abstract

Cisplatin is a drug widely used in chemotherapy that frequently causes severe renal dysfunction. Organic transporters have an important role to control the absorption and excretion of cisplatin in renal cells. Deletion and blockage of kinin B1 receptor has already been show to protect against cisplatin-induced acute kidney injury. To test whether it exerts its protective function by modulating the organic transporters in kidney, we studied kinin B1 receptor knockout mice and treatment with a receptor antagonist at basal state and in presence of cisplatin. Cisplatin administration caused downregulation of renal organic transporters; in B1 receptor knockout mice, this downregulation of organic transporters in kidney was absent; and treatment by a B1 receptor antagonist attenuated the downregulation of the transporter MATE-1. Moreover, kinin B1 receptor deletion and blockage at basal state resulted in higher renal expression of MATE-1. Moreover we observed that kinin B1 receptor deletion and blockage result in less accumulation of platinum in renal tissue. Thus, we propose that B1 receptor deletion and blockage protect the kidney from cisplatin-induced acute kidney injury by upregulating the expression of MATE-1, thereby increasing the efflux of cisplatin from renal cells.

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Acknowledgements

This work was supported by FAPESP grants 2013/06207-6, 2015/20082-7 and by CAPES/PROBRAL grant 7191/15-4.

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Authors and Affiliations

  1. Department of Biophysics, Federal University of São Paulo, Rua Pedro de Toledo, 669 9 Andar, 04039-032, São Paulo, SP, Brazil

    Gabriel R. Estrela, Frederick Wasinski & Ronaldo C. Araujo

  2. Department of Medicine, Division of Nephrology, Federal University of São Paulo, 04023-900, São Paulo, SP, Brazil

    Gabriel R. Estrela, Frederick Wasinski, Raphael J. F. Felizardo & Ronaldo C. Araujo

  3. Department of Immunology, Laboratory of Transplantation Immunobiology, Institute of Biomedical Sciences, University of São Paulo, 05508-900, São Paulo, SP, Brazil

    Niels O. S. Câmara

  4. Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany

    Laura L. Souza & Michael Bader

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  1. Gabriel R. Estrela
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  2. Frederick Wasinski
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  3. Raphael J. F. Felizardo
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  7. Ronaldo C. Araujo
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Correspondence to Ronaldo C. Araujo.

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Estrela, G.R., Wasinski, F., Felizardo, R.J.F. et al. MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells. Mol Cell Biochem 428, 101–108 (2017). https://doi.org/10.1007/s11010-016-2920-x

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  • DOI: https://doi.org/10.1007/s11010-016-2920-x

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