Guo Junxia, Gao Ya, Cao Xuelian, Zhang Jing, Chen Wen
Food Science Department, College of Biochemical Engineering, Beijing Union University, Fatou west 18#, Chaoyang District, Beijing, 100023, People's Republic of China.
Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, 100191, People's Republic of China.
Lipids Health Dis. 2017 Mar 16;16(1):56. doi: 10.1186/s12944-017-0444-3.
A number of studies indicate that taurine promotes cholesterol conversion to bile acids by upregulating CYP7A1 gene expression. Few in vitro studies are concerned the concentration change of cholesterol and its product of bile acids, and the molecular mechanism of CYP7A1 induction by taurine.
The levels of intracellular total cholesterol (TC), free cholesterol (FC), cholesterol ester (EC), total bile acids (TBA) and medium TBA were determined after HepG2 cells were cultured for 24/48 h in DMEM supplemented with taurine at the final concentrations of 1/10/20 mM respectively. The protein expressions of CYP7A1, MEK1/2, c-Jun, p-c-Jun and HNF-4α were detected.
Taurine significantly reduced cellular TC and FC in dose -and time-dependent ways, and obviously increased intracellular/medium TBA and CYP7A1 expressions. There was no change in c-Jun expression, but the protein expressions of MEK1/2 and p-c-Jun were increased at 24 h and inhibited at 48 h by 20 mM taurine while HNF4α was induced after both of the 24 h and 48 h treatment.
Taurine could enhance CYP7A1 expression by inducing HNF4α and inhibiting MEK1/2 and p-c-Jun expressions to promote intracellular cholesterol metabolism.
多项研究表明，牛磺酸通过上调CYP7A1基因表达促进胆固醇转化为胆汁酸。很少有体外研究关注胆固醇及其胆汁酸产物的浓度变化，以及牛磺酸诱导CYP7A1的分子机制。
将HepG2细胞分别在终浓度为1/10/20 mM牛磺酸的DMEM中培养24/48小时后，测定细胞内总胆固醇（TC）、游离胆固醇（FC）、胆固醇酯（EC）、总胆汁酸（TBA）和培养基中TBA的水平。检测CYP7A1、MEK1/2、c-Jun、p-c-Jun和HNF-4α的蛋白表达。
牛磺酸以剂量和时间依赖性方式显著降低细胞内TC和FC，并明显增加细胞内/培养基中TBA和CYP7A1的表达。c-Jun表达无变化，但20 mM牛磺酸在24小时时增加MEK1/2和p-c-Jun的蛋白表达，在48小时时抑制其表达，而在24小时和48小时处理后均诱导HNF4α表达。
牛磺酸可通过诱导HNF4α并抑制MEK1/2和p-c-Jun表达来增强CYP7A1表达，从而促进细胞内胆固醇代谢。
