活化的AMPK解释了硫酸化低分子量古罗糖醛酸对HepG2细胞的降血脂作用。
Activated AMPK explains hypolipidemic effects of sulfated low molecular weight guluronate on HepG2 cells.
作者信息
Liu Xin, Hao Jie-Jie, Zhang Li-Juan, Zhao Xia, He Xiao-Xi, Li Miao-Miao, Zhao Xiao-Liang, Wu Jian-Dong, Qiu Pei-Ju, Yu Guang-Li
机构信息
Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
出版信息
Eur J Med Chem. 2014 Oct 6;85:304-10. doi: 10.1016/j.ejmech.2014.07.107. Epub 2014 Jul 30.
Low molecular weight and sulfated low molecular weight guluronate (LMG and SLMG) were prepared and hypolipidemic effects were studied in a human hepatocellular carcinoma HepG2 cell line. Both compounds decreased total cholesterol (TC) and triglycerides (TG) and inhibited 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity in HepG2 cells. In general, SLMG had greater effects than LMG. Activation of sterol regulatory element-binding protein 2 (SREBP-2), low density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK), and AMPK's downstream targets were evidenced by increased phosphorylation of AMPK, HMGCR, and acetyl-CoA-carboxylase (ACC), which decreased HMGRC and ACC activity. We further demonstrated that activated AMPK was linked to down-regulated SREBP-1 and up-regulated cholesterol 7α-hydroxylase (CYP7A1).
制备了低分子量和硫酸化低分子量古洛糖醛酸（LMG和SLMG），并在人肝癌HepG2细胞系中研究了它们的降血脂作用。两种化合物均降低了总胆固醇（TC）和甘油三酯（TG），并抑制了HepG2细胞中3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的活性。一般来说，SLMG的作用比LMG更强。固醇调节元件结合蛋白2（SREBP-2）、低密度脂蛋白受体（LDLR）、AMP激活蛋白激酶（AMPK）及其下游靶点的激活表现为AMPK、HMGCR和乙酰辅酶A羧化酶（ACC）磷酸化增加，这降低了HMGRC和ACC的活性。我们进一步证明，激活的AMPK与SREBP-1下调和胆固醇7α-羟化酶（CYP7A1）上调有关。
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