Oxidized low-density lipoprotein decreases the induced nitric oxide synthesis in rat mesangial cells.
Recently, the close relation between oxidized low density lipoprotein (Ox-LDL) and the progression of glomerular injury has been demonstrated. The nitric oxide (NO) pathway in glomerular mesangial cells may be a potential target for the adverse effects of Ox-LDL in the development of glomerular injury. In this study, we treated cultured rat mesangial cells (RMC) with Fe(2+)-oxidized LDL and then stimulated the cells with lipopolysacharride (LPS, 10 micrograms ml-1). The LPS-induced NO production, assessed by NO2-concentrations in cultured supernatants, decreased from 7.83 nmol per 10(6) cells in control to 4.00 nmol per 10(6) cells and 1.67 nmol per 10(6) cells in RMC preincubated with Ox-LDL at 20 micrograms ml-1 and 40 micrograms ml-1, respectively (P < 0.01). Native LDL had no significant effects on LPS-induced NO production. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we could not detect significant alteration of inducible NO synthase (iNOS) mRNA levels in RMC preincubated with Ox-LDL. Our results suggest that Ox-LDL decreases induced NO production in RMC, which may contribute to the adverse effects of Ox-LDL in progressive glomerular injury. The mechanisms of this decrease may not involve changes of iNOS genic transcription.
Wu
Z L
ZL
Division of Nephrology, Zhong Shan Hospital, Shanghai, P.R. China.
Liang
M Y
MY
Qiu
L Q
LQ
D000818:Animals; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D007674:Kidney Diseases / Q000209:etiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D009573:Nitrites; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat