The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지

Cisplatin-induced Alterations of $Na^+$-dependent Phosphate Uptake in Renal Epithelial Cells

  • Lee, Sung-Ju (Department of Physiology, College of Medicine, Pusan National University) ;
  • Kwon, Chae-Hwa (Department of Physiology, College of Medicine, Pusan National University) ;
  • Kim, Yong-Keun (Department of Physiology, College of Medicine, Pusan National University)
  • Published : 2007.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Cisplatin treatment increases the excretion of inorganic phosphate in vivo. However, the mechanism by which cisplatin reduces phosphate uptake through renal proximal tubular cells has not yet been elucidated. We examined the effect of cisplatin on $Na^+$-dependent phosphate uptake in opossum kidney (OK) cells, an established proximal tubular cell line. Cells were exposed to cisplatin for an appropriate time period and phosphate uptake was measured using $[^{32}P]$-phosphate. Changes in the number of phosphate transporter in membranes were evaluated by kinetic analysis, $[^{14}C]$phosphonoformic acid binding, and Western blot analysis. Cisplatin inhibited phosphate uptake in a time- and dose-dependent manner, and also the $Na^+$-dependent uptake without altering $Na^+$-independent uptake. The cisplatin inhibition was not affected by the hydrogen peroxide scavenger catalase, but completely prevented by the hydroxyl radical scavenger dimethylthiourea. Antioxidants were ineffective in preventing the cisplatin-induced inhibition of phosphate uptake. Kinetic analysis indicated that cisplatin decreased Vmax of $Na^+$-dependent phosphate uptake without any change in the Km value. $Na^+$-dependent phosphonoformic acid binding was decreased by cisplatin treatment. Western blot analysis showed that cisplatin caused degradation of $Na^+$-dependent phosphate transporter protein. Taken together, these data suggest that cisplatin inhibits phosphate transport in renal proximal tubular cells through the reduction in the number of functional phosphate transport units. Such effects of cisplatin are mediated by production of hydroxyl radicals.

Keywords

References

  1. Baliga R, Zhang Z, Baliga M, Ueda N, Shah SV. In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int 53: 394-401, 1998 https://doi.org/10.1046/j.1523-1755.1998.00767.x
  2. Borch RF. The platinum antitumor drugs. In: Powis G, Prough RA ed, Metabolism & Action of Anticancer Drugs. 1st ed. Taylor & Francis, London, p 163-193, 1987
  3. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254, 1976 https://doi.org/10.1016/0003-2697(76)90527-3
  4. Campbell AB, Kalman SM, Jacobs C. Plasma platinum levels: relationship to cisplatin dose and nephrotoxicity. Cancer Treat Rep 67: 169-172, 1983
  5. Caverzasio J, Rizzoli R, Bonjour JP. Sodium-dependent phosphate transport inhibited by parathyroid hormone and cyclic AMP stimulation in an opossum kidney cell line. J Biol Chem 261: 3233-3237, 1986
  6. Courjault-Gautier F, Hoet D, Leroy D, Toutain HJ. Dissimilar alterations of sodium-coupled uptake by platinum-coordination complexes in renal proximal tubular cells in primary culture. J Pharmacol Exp Ther 270: 1097-1104, 1994
  7. Cummings BS, Schnellmann RG. Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther 302: 8-17, 2002 https://doi.org/10.1124/jpet.302.1.8
  8. Dumas M, d'Athis P, de Gislain C, Escousse A, Guerrin J, Autissier N. Model independent pharmacokinetic study of cis-dichlorodiammineplatinum (II). Int J Clin Pharmacol Ther Toxicol 23: 430-433, 1985
  9. Fiske CH, SubbaRow Y. The colorimetric determination of phosphorus. J Biol Chem 66: 375-400, 1925
  10. Garnick MB, Mayer RJ, Abelson HT. Acute renal failure associated with cancer treatment. In: Brenner BM, Lazarus JM ed, Acute Renal Failure. 1st ed. Churchill Livingtone, New York, p 621- 657, 1988
  11. Greger R, Lang F, Marchand G, Knox FG. Site of renal phosphate reabsorption. Micropuncture and microinfusion study. Pflugers Arch 369: 111-118, 1977 https://doi.org/10.1007/BF00591566
  12. Hammerman MR. Phosphate transport across renal proximal tubular cell membranes. Am J Physiol 251: F385-F398, 1986
  13. Hilfiker H, Hattenhauer O, Traebert M, Forster I, Murer H, Biber J. Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine. Proc Natl Acad Sci USA 95: 14564-14569, 1998
  14. Hoppe A, Lin JT, Onsgard M, Knox FG, Dousa TP. Quantitation of the Na(+)-Pi cotransporter in renal cortical brush border membranes. [$^{14}$CJphosphonoformic acid as a useful probe to determine the density and its change in response to parathyroid hormone. J Biol Chem 266: 11528-11536, 1991
  15. Ikeda K, Kajiwara K, Tanabe E, Tokumaru S, Kishida E, Masuzawa Y, Kojo S. Involvement of hydrogen peroxide and hydroxyl radical in chemically induced apoptosis of HL-60 cells. Biochem Pharmacol 57: 1361-1365, 1999 https://doi.org/10.1016/S0006-2952(99)00055-6
  16. Kim YK, Byun HS, Kim YH, Woo JS, Lee SH. Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption. Toxicol Appl Pharmacol 130: 19-26, 1995 https://doi.org/10.1006/taap.1995.1003
  17. Kim YK, Kim HJ, Kwon CH, Kim JH, Woo JS, Jung Js, Kim JM. Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol 25: 374-382, 2005 https://doi.org/10.1002/jat.1081
  18. Koppenol WH. Generation and thermodynamic properties of oxyradicals. In: Vigo-Pelfery C ed, Membrane Lipid Oxidation. 1st ed. CRC Press, Boca Raton, p 1-10, 1993
  19. Leonard BJ, Eccleston E, Jones D, Todd P, Walpole A. Antileukemic and nephrotoxic properties of platinum compounds. Nature 234: 43, 1971
  20. Levi M, Cronin RE. Early selective effects of gentamicin on renal brush-border membrane Na-Pi cotransport and Na-H exchange. Am J Physiol 258: F1379-F1387, 1990
  21. Lieberthal W, Triaca V, Levine J. Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis. Am J Physiol 270: F700-708, 1996
  22. Lippman AJ, Helson C, Helson L, Krakoff IH. Clinical trials of cis-diamminedichloroplatinum (NSC-119875). Cancer Chemother Rep 57: 191-200, 1973
  23. Loghman-Adham M. Inhibition of renal Na(+)-Pi cotransporter by mercuric chloride: role of sulfhydryl groups. J Cell Biochem 49: 199-207, 1992 https://doi.org/10.1002/jcb.240490212
  24. Loghman-Adham M, Motock GT. Stimulation of P(i) transport in opossum kidney cells by hyposmotic media. Am J Physiol 264: F585-F592, 1993
  25. Madias NE, Harrington JT. Platinum nephrotoxicity. Am J Med 65: 307-314, 1978 https://doi.org/10.1016/0002-9343(78)90825-2
  26. Min SK, Kim SY, Kim CH, Woo JS, Jung JS, Kim YK. Role of lipid peroxidation and poly (ADP-ribose) polymerase activation in oxidant-induced membrane transport dysfunction in opposum kidney (OK) cells. Toxicol Appl Pharmacol 166: 196-202, 2000 https://doi.org/10.1006/taap.2000.8956
  27. Mitchell P. Strategy of research on the chemiosmotic mechanism of cytochrome oxidase. FEBS Lett 231: 270-271, 1988 https://doi.org/10.1016/0014-5793(88)80746-4
  28. Murer H, Hernando N, Forster I, Biber J. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 80: 1373-1409, 2000 https://doi.org/10.1152/physrev.2000.80.4.1373
  29. Neame KD, Richards TG. Elementary Kinetics of Membrane Carrier Transport. 1st ed. Blackwell Scientific Publications, New York, p 1972
  30. Park K, Kim KR, Kim JY, Park YS. Effect of cadmium on Na-Pi cotransport kinetics in rabbit renal brush-border membrane vesicles. Toxicol Appl Pharmacol 145: 255-259, 1997 https://doi.org/10.1006/taap.1997.8180
  31. Pfister MF, Hilfiker H, Forgo J, Lederer E, Biber J, Murer H. Cellular mechanisms involved in the acute adaptation of OK cell Na/Pi-cotransport to high- or low-Pi medium. Pflugers Arch 435: 713-719, 1998 https://doi.org/10.1007/s004240050573
  32. Pfister MF, Lederer E, Forgo J, Ziegler U, Lotscher M, Quabius ES, Biber J, Murer H. Parathyroid hormone-dependent degradation of type II Na+/Pi cotransporters. J Biol Chem 272: 20125- 20130, 1997 https://doi.org/10.1074/jbc.272.32.20125
  33. Sorribas V, Markovich D, Hayes G, Stange G, Forgo J, Biber J, Murer H. Cloning of a Na/Pi cotransporter from opossum kidney cells. J Biol Chem 269: 6615-6621, 1994
  34. Szczepanska KM, Yusufi AN, Dousa TP. Interactions of [$^{14}$CJphosphonoformic acid with renal cortical brush-border membranes. Relationship to the Na+-phosphate co-transporter. J Biol Chem 262: 8000-8010, 1987
  35. Szczepanska KM, Yusufi AN, Lin JT, Dousa TP. Structural requirement of monophosphates for inhibition of Na+-Pi cotransport in renal brush border membrane. Biochem Pharmacol 38: 4191-4197, 1989 https://doi.org/10.1016/0006-2952(89)90514-5
  36. Szczepanska KM, Yusufi AN, VanScoy M, Webster SK, Dousa TP. Phosphonocarboxylic acids as specific inhibitors of Na+- dependent transport of phosphate across renal brush border membrane. J Biol Chem 261: 6375-6383, 1986
  37. Ullrich KJ, Rumrich G, Kloss S. Phosphate transport in the proximal convolution of the rat kidney. I. Tubular heterogeneity, effect of parathyroid hormone in acute and chronic parathyroidectomized animals and effect of phosphate diet. Pflugers Arch 372: 269-274, 1977 https://doi.org/10.1007/BF01063862
  38. Von Hoff DD, Schilsky R, Reichert CM, Reddick RL, Rozencweig M, Young RC, Muggia FM. Toxic effects of cis-dichlorodiammineplatinum (II) in man. Cancer Treat Rep 63: 1527-1531, 1979
  39. Wang X, Martindale JL, Holbrook NJ. Requirement for ERK activation in cisplatin-induced apoptosis. J Biol Chem 275: 39435-39443., 2000 https://doi.org/10.1074/jbc.M004583200
  40. Yusufi AN, Szczepanska KM, Hoppe A, Dousa TP. Different mechanisms of adaptive increase in Na+-Pi cotransport across renal brush-border membrane. Am J Physiol 256: F852-F861, 1989