Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL.
In protein-uric states, renal tubular epithelial cells are exposed to diverse macromolecules, including low-density 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 injuries renal tubular epithelial cells (LLC-PK1). We demonstrate that the cytotoxicity of LDLox on LLC-PK1 cells resembles its toxicity to human umbilical vein 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.
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
A
A
Agarwal
J
J
Balla
G
G
Balla
A J
AJ
Croatt
G M
GM
Vercellotti
K A
KA
Nath
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001761:Bleomycin; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000494:pharmacology*; D013552:Swine
D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D001761:Bleomycin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)