RENAL TUBULAR EPITHELIAL-CELLS MIMIC ENDOTHELIAL-CELLS UPON EXPOSURE TO OXIDIZED LDL

In proteinuric states, renal tubular epithelial cells are exposed to d iverse macromolecules, including low-density lipoproteins (LDL), norma lly excluded from the urinary space. Oxidized LDL (LDL(ox)) is incrimi nated in atherogenesis and glomerulosclerosis. Since urine is prooxida nt, we considered whether LDL(ox) injures renal tubular epithelial cel ls (LLC-PK1). We demonstrate that the cytotoxicity of LDL(ox) on LLC-P K1 cells resembles its toxicity to human umbilical vein endothelial ce lls (HUVEC) in that oxidized but not native LDL is injurious. Pretreat ment of LLC-PK1 cells and HUVEC with antioxidants markedly reduced the cytotoxicity of LDL(ox). Pretreatment of LDL with anti-oxidants, prio r to oxidation of LDL, vitiated its cytotoxicity. That LDL(ox) is proo xidant was supported by expression of heme oxygenase, a redox-sensitiv e enzyme. LDL(ox) induced heme oxygenase mRNA and enzyme activity. Pre treatment of LDL with antioxidants prior to oxidation attenuated heme oxygenase mRNA induction in LLC-PK1 and HUVEC. An iron chelator preven ted cytotoxicity and heme oxygenase expression induced by LDL(ox). Bas ed on these effects of LDL(ox), we draw an analogy between tubulointer stitial disease and atherogenesis and speculate that LDL(ox) contribut es to tubulointerstitial disease in proteinuric states.