TY - JOUR
T1 - Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL
AU - Agarwal, Anupam
AU - Balla, József
AU - Balla, György
AU - Croatt, Anthony J.
AU - Vercellotti, Gregory M.
AU - Nath, Karl A.
PY - 1996
Y1 - 1996
N2 - 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 injures 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.
AB - 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 injures 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.
KW - Atherosclerosis
KW - Heme oxygenase
KW - Iron
KW - Proteinuria
KW - Renal tubule
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U2 - 10.1152/ajprenal.1996.271.4.f814
DO - 10.1152/ajprenal.1996.271.4.f814
M3 - Article
C2 - 8898011
AN - SCOPUS:0029958197
VL - 271
SP - F814-F823
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 0002-9513
IS - 4 40-4
ER -