Tan Yan Qin, Wong Tsz Yan, Lin Shu-Mei, Leung Lai K
Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong Kong.
Department of Food Science, National Chiayi University, Chiayi City, Taiwan, ROC.
Mol Cell Biochem. 2017 Jan;424(1-2):163-172. doi: 10.1007/s11010-016-2851-6. Epub 2016 Oct 24.
Consumption of fruits and vegetables is generally regarded as beneficial to plasma lipid profile. The mechanism by which the plant foods induce desirable lipid changes remains unclear. SREBP-2 is crucial in cholesterol metabolism, and it is a major regulator of the cholesterol biosynthesis enzyme HMGCR. Our lab has previously illustrated that apigenin and luteolin could attenuate the nuclear translocation of SREBP-2 through an AMPK-dependent pathway. In the present study, these two flavones were studied for their ability to deter the same in an AMPK-independent signaling route. The processing of SREBP-2 protein was promoted by phorbol 12-myristate 13-acetate (PMA) in the hepatic cells WRL and HepG2, and the increased processing was reversed by apigenin or luteolin co-administration. EMSA results demonstrated that the PMA-induced DNA-binding activity was weakened by the flavones. The increased amount of nuclear SREBP-2 in cells was attenuated by the flavonoid as shown by immunocytochemical imaging. Quantitative reverse transcriptase-polymerase chain reaction assay demonstrated that the transcription of HMGCR under both flavone treatments was reduced. However, apigenin appeared to be stronger than luteolin in restraining PMA-induced HMGCR mRNA expression. Since PMA is a diacylglycerol analog, these findings might have some physiological implications.
食用水果和蔬菜通常被认为对血浆脂质谱有益。植物性食物引起理想脂质变化的机制尚不清楚。固醇调节元件结合蛋白-2（SREBP-2）在胆固醇代谢中起关键作用，并且是胆固醇生物合成酶3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的主要调节因子。我们实验室先前已经证明，芹菜素和木犀草素可以通过一种依赖于腺苷酸活化蛋白激酶（AMPK）的途径减弱SREBP-2的核转位。在本研究中，研究了这两种黄酮在一条不依赖AMPK的信号通路中阻止相同情况发生的能力。佛波醇12-肉豆蔻酸酯13-乙酸（PMA）在肝细胞WRL和HepG2中促进了SREBP-2蛋白的加工过程，而芹菜素或木犀草素共同给药可逆转这种增加的加工过程。电泳迁移率变动分析（EMSA）结果表明，黄酮类化合物减弱了PMA诱导的DNA结合活性。免疫细胞化学成像显示，黄酮类化合物减弱了细胞中核SREBP-2数量的增加。定量逆转录聚合酶链反应分析表明，在两种黄酮处理下HMGCR的转录均降低。然而，在抑制PMA诱导的HMGCR mRNA表达方面，芹菜素似乎比木犀草素更强。由于PMA是一种二酰基甘油类似物，这些发现可能具有一些生理学意义。
