Kang Jing, Cheng Bei, Jiang Lei
Department of Geriatrics, the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Sheng Li Xue Bao. 2010 Oct 25;62(5):427-32.
The aim of the present study was to investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction pathway in the expression of ATP binding cassette transporter A1 (ABCA1) and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) induced by visfatin and to discuss the mechanism of foam cell formation induced by visfatin. THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate (PMA) for 48 h, and then the macrophages were exposed to visfatin and PPARγ activator rosiglitazone, respectively. The expressions of PPARγ, ABCA1 and ACAT1 mRNA and protein were determined by RT-PCR and Western blot respectively. The contents of total cholesterol (TC) and free cholesterol (FC) were detected by enzyme fluorescence analysis. The content of cholesterol ester (CE) was calculated by the difference between TC and FC. The results showed that visfatin decreased the mRNA and protein expressions of PPARγ and ABCA1, increased the mRNA and protein expressions of ACAT1, and increased the contents of FC and CE in a concentration-dependent manner. These above effects of visfatin were inhibited by rosiglitazone in a concentration-dependent manner. These results suggest that visfatin may down-regulate the ABCA1 expression and up-regulate the ACAT1 expression via PPARγ signal transduction pathway, which decreases the outflow of FC, increases the content of CE, and then induces foam cell formation.
本研究旨在探讨过氧化物酶体增殖物激活受体γ(PPARγ)信号转导通路在visfatin诱导的ATP结合盒转运体A1(ABCA1)和酰基辅酶A:胆固醇酰基转移酶1(ACAT1)表达中的作用,并探讨visfatin诱导泡沫细胞形成的机制。用160 nmol/L佛波酯(PMA)将THP-1单核细胞诱导为巨噬细胞48小时,然后将巨噬细胞分别暴露于visfatin和PPARγ激动剂罗格列酮。分别用RT-PCR和Western blot检测PPARγ、ABCA1和ACAT1 mRNA及蛋白的表达。用酶荧光分析法检测总胆固醇(TC)和游离胆固醇(FC)的含量。通过TC与FC的差值计算胆固醇酯(CE)的含量。结果显示,visfatin以浓度依赖性方式降低PPARγ和ABCA1的mRNA及蛋白表达,增加ACAT1的mRNA及蛋白表达,并增加FC和CE的含量。罗格列酮以浓度依赖性方式抑制visfatin的上述作用。这些结果表明,visfatin可能通过PPARγ信号转导通路下调ABCA1表达并上调ACAT1表达,从而减少FC流出,增加CE含量,进而诱导泡沫细胞形成。