Rosiglitazone inhibits expression of acyl-coenzyme A:cholesterol acyltransferase-1 in THP-1 macrophages induced by advanced glycation end-products

摘要

Objective:To investigate the effects of rosiglitazone,a synthetic ligand of peroxisome proliferators-activated receptor gamma(PPARγ),on the expression of acyl-coenzyme A:cholesterol acyltransferase-1(ACAT-1) in phorbol myristate acetate(PMA)-pretreated THP-1 cells after the inducement of advanced glycation end products(AGEs).Methods:After THP-1 cells were cultured in the presence of 0.1 μmol/L PMA for 72 h to induce phagocytic differentiation,the obtained THP-1 macrophages were treated with rosiglitazone for 4 h at different concentrations(1,5 or 10 μmol/L) and then exposed to AGEs-modified bovine serum albumin(AGEs-BSA) for 24 h at a concentration of 200 mg/L.Reverse transcription polymerase chain reaction(RT-PCR) and Western blot analysis were performed to detect the mRNA and protein expressions of ACAT-1 respectively.Results:Administration of AGEs-BSA(200 mg/L) into the THP-1 macrophages resulted in up-regulation of ACAT-1 at mRNA and protein levels when compared with the expressions in macrophages incubated with serum-free RPMI1640.Pretreatment of rosiglitazone inhibited significantly the increased expression of ACAT-1 induced by AGEs-BSA in a concentration-dependent manner.Conclusion:PPARγ activation by rosiglitazone down-regulates ACAT-1 expression induced by AGEs in THP-1 macrophages,which might provide a new way for treating atherogenesis in diabetic patients.