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

• Published in: Journal of Medical Colleges of PLA 2008, Vol.23 (3), p.127-136
• Main Authors: Qihong, Yang, Qiang, Xu, Hong, Zhang, Liangyi, Si
• Format: Article
• Language: English
• Subjects: Acyl-coenzyme A: cholesterol acyltransferase-1; Advanced glycation end products; Gene expression; Rosiglitazone; 基因表达; 糖化终产物; 糖尿病; 老年人; 胆固醇酰基转移酶-1; 酰基辅酶A
• ISSN: 1000-1948
• DOI: 10.1016/S1000-1948(08)60034-9

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： PPARy 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.