Toxicity of holotransferrin but not albumin in proximal tubule cells in primary culture.

Journal of the American Society of Nephrology : JASN
L ChenD C Harris

Abstract

Proteinuria has been invoked as a cause of tubulointerstitial injury in chronic renal disease, and in vivo studies have suggested indirectly the particular nephrotoxicity of one urinary protein holotransferrin (Tf-Fe). However, to date there has been no direct evidence for the nephrotoxicity of Tf-Fe. To examine the potential cytotoxicity of Tf-Fe and the mechanism involved, and to compare this to another urinary protein albumin, rat proximal tubule cells were studied in primary culture. Tf-Fe at pH 6.0 caused functional and ultrastructural injury, but no cytotoxicity was seen with cells exposed to albumin, apotransferrin (transferrin), or Tf-Fe at pH 7.4. The influence of pH on Tf-Fe-induced cytotoxicity was not due to pH per se, but could be explained by an effect on Tf-Fe uptake. At pH 6.0, uptake of 125I-Tf-Fe (3.55 +/- 0.05 versus 1.25 +/- 0.10 fmol/dish, P < 0.01) and intracellular iron concentration (1.14 +/- 0.25 versus 0.46 +/- 0.23 nmol/dish, P < 0.01) were increased compared with values at pH 7.4. In contrast, pH 6.0 did not increase iron uptake from FeCl3. Lysine (100 mM) inhibited Tf-Fe uptake, decreased intracellular iron concentration, and attenuated Tf-Fe-induced cytotoxicity. The iron chelator des-ferrioxamine ...Continue Reading

Citations

Jan 28, 1999·The Journal of Biological Chemistry·J D StockandD C Eaton
Dec 20, 2000·Biochimie·J Gburek, J Osada
Mar 29, 2002·Kidney International·Yiping WangDavid C H Harris
May 7, 1999·Kidney International·G A EppelW D Comper
Jun 11, 1999·Journal of the American Society of Nephrology : JASN·Y WangD C Harris
Jun 26, 2002·Kidney International·François Canonne-Hergaux, Philippe Gros
Jul 25, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Atsuko Kamijo-IkemoriKenjiro Kimura
May 26, 2006·European Journal of Anaesthesiology·I J Davidson
Nov 6, 2007·Journal of the American Society of Nephrology : JASN·Yuji KamijoToshifumi Aoyama
Feb 18, 2003·The Journal of Clinical Investigation·Sydney TangKar Neng Lai
Jan 3, 2001·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·S TangS H Sacks
Dec 1, 2001·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·A J LangoneA B Fogo

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