Title: Probucol Inhibits Transforming Growth Factor-β_1 Expression Induced by Oxidized LDL in Rat Mesangial Cells
Abstract: Purpose To investigate the effects of probucol on AP-1 binding activity and expression of transforming growth factor β 1(TGF-β 1) by oxidized LDL in mesagngial cells and clarify the possible molecular mechanisms of antioxidant in lipid-induced glomerular injury. Methods Rat mesangial cells were randomized to divided into three groups:normal cells,ox-LDL-treated cells and probucol+ox-LDL-treated cells.AP-1 binding in mesangial cells was measured by gel shift assay.The protein expression of c-Jun and TGF-β 1,and the phosphorylation of JNK/SAPK were detected by Western blot analysis.The expression of TGF-β 1 mRNA was detected by Northern blot analysis. Results A 20-hour treatment with probucol (50 μmol/L) was applied prior to 24-hour incubation of ox-LDL in mesangial cells.It was found that AP-1 binding had no difference between probucol-treated normal cells and normal ones,but probucol at 50 μmol/L appreciably reduced the ox-LDL-induced AP-1 binding.Probucol at 50,100,200 μmol/L significantly inhibited the phosphorylation of JNK 1/SAPK after being exposed to ox-LDL(100 μg/mL) for 30 min in mesangial cells.Probucol at 50,100,200 μmol/L reduced c-Jun expression induced by ox-LDL.Ox-LDL at 10 μg/mL did not stimulate TGF-β 1 mRNA expression,but when ox-LDL rose to 50,100 μg/mL,TGF-β 1 mRNA expression increased 1.8 and 1.9 times,respectively.Simultaneously,ox-LDL stimulated the expression of TGF-β 1 protein markedly.After being exposed to probucol,the ox-LDL-induced expression of TGF-β 1 mRNA and protein decreased significantly (P0.05). Conclusions Probucol downregulates the expression of TGF-β 1 mRNA and protein induced by ox-LDL in mesangial cells,possibly through the inhibition of the phosphorylation of JNK 1/SAPK and AP-1 binding activity.
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
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