α-Tocopherol Inhibits Activator Protein-1 Binding and TGF-β1 Expression Induced by High Glucose in Rat Mesangial Cells / 复旦学报（医学版）

ABSTRACT

Purpose　To study the effects of α-tocopherol on activator protein-1(AP-1)binding and TGF-β1 expression induced by high glucose in rat mesangial cells and further to clarify the molecular mechanism of antioxidant in treating diabetic nephropathy.　Methods　AP-1 binding of the rat mesangial cells exposed to high glucose was detected by gel shift assay.The Jun,Fos compositions of AP-1 dimer were determined by supershift assay.Protein expression of TGF-β1 was detected by Western blot.Additionally,the effects of α-tocopherol on AP-1 binding and TGF-β1 expression induced by glucose in rat mesangial cells were also studied.　Results　High glucose stimulated AP-1 binding of mesangial cells in time-and-dose-dependent manners .This AP-1 binding increase involved JunD and Fos as shown by gel supershift.Glucose also increased protein expression of TGF-β1 at same time.The increased AP-1 binding and TGF-β1 were inhibited with pretreatment with α-tocopherol in glucose-treated mesangial cells.　Conclusions　This study suggests that α-tocopherol can significantly inhibit AP-1 activity and TGF-β1 expression by glucose in rat mesangial cells,which may be one of its antioxidation mechanisms to retard diabetic nephropathy.