Nagao Sachi, Murao Koji, Imachi Hitomi, Cao Wen-Ming, Yu Xiao, Li Junhua, Matsumoto Kensuke, Nishiuchi Takamasa, Ahmed Rania A M, Wong Norman C W, Ueda Kazumitsu, Ishida Toshihiko
Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
FEBS Lett. 2006 Aug 7;580(18):4371-6. doi: 10.1016/j.febslet.2006.07.001. Epub 2006 Jul 10.
The ATP-binding cassette transporter A1 (ABCA1) regulates lipid efflux from peripheral cells to High-density lipoprotein. The platelet-derived growth factor (PDGF) is a potent mitogen that enables vascular smooth muscle cells to participate in atherosclerosis. In this report, we showed that PDGF suppressed endogenous expression of ABCA1 in cultured vascular smooth muscle cells. Exposure of CRL-208 cells to PDGF elicited a rapid phosphorylation of a kinase downstream from PI3-K, Akt. The constitutively active form of both p110, a subunit of PI3-K, and Akt inhibited activity of the ABCA1 promoter. In conclusion, PI3-K-Akt pathways participate in PDGF-suppression of ABCA1 expression.
ATP结合盒转运蛋白A1（ABCA1）调节脂质从外周细胞外流至高密度脂蛋白。血小板衍生生长因子（PDGF）是一种有效的促有丝分裂原，可使血管平滑肌细胞参与动脉粥样硬化。在本报告中，我们表明PDGF抑制培养的血管平滑肌细胞中ABCA1的内源性表达。将CRL-208细胞暴露于PDGF会引发PI3-K下游激酶Akt的快速磷酸化。PI3-K的亚基p110和Akt的组成型活性形式均抑制ABCA1启动子的活性。总之，PI3-K-Akt途径参与了PDGF对ABCA1表达的抑制作用。
