Renal tubular epithelial cells mimic endothelial cells upon
exposure to oxidized ldl.
Agarwal, Anupam, J[acute]ozsef Balla, Gy[diaeresis]orgy Balla, Anthony
J. Croatt, Gregory M. Vercellotti, Karl A. Nath.
Department of Medicine, University of Minnesota Medical School,
Minneapolis, Minnesota, Departments of Medicine and Pediatrics,
University of Debrecen, Debrecen, Hungary
APStracts 3:0114F, 1996.
In proteinuric states, renal tubular epithelial cells are exposed to
diverse macromolecules - including lipoproteins (LDL) - normally
excluded from the urinary space. Oxidized LDL (LDLox) is incriminated
in atherogenesis and glomerulosclerosis. Since urine is prooxidant,
we considered whether LDLox injures renal tubular epithelial cells
(LLC-PK1). We demonstrate that the cytotoxicity of LDLox on LLC-PK1
cells resembles its toxicity to endothelial cells (HUVEC) in that
oxidized but not native LDL is injurious. Pretreatment of LLC-PK1
cells and HUVEC with antioxidants markedly reduced the cytotoxicity
of LDLox. Pretreatment of LDL with antioxidants, prior to oxidation
of LDL, vitiated its cytotoxicity. That LDLox is prooxidant was
supported by expression of heme oxygenase, a redox sensitive enzyme.
LDLox induced heme oxygenase mRNA and enzyme activity. Pretreatment
of LDL with antioxidants prior to oxidation attenuated heme oxygenase
mRNA induction in LLC-PK1 and HUVEC. An iron chelator prevented
cytotoxicity and heme oxygenase expression induced by LDLox. Based on
these effects of LDLox, we draw an analogy between tubulointerstitial
disease and atherogenesis and speculate that LDLox contributes to
tubulointerstitial disease in proteinuric states.
Received 5 October 1995; accepted in final form 17 June 1996.
APS Manuscript Number F334-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96