Galli C, Risé P, Marangoni F, Petroni A, Visioli F
Institute of Pharmacological Sciences, School of Pharmacy, University of Milan, Italy.
Prostaglandins Leukot Essent Fatty Acids. 1997 Jul;57(1):23-6. doi: 10.1016/s0952-3278(97)90488-9.
We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.
我们研究了长链多不饱和脂肪酸（LC-PUFA）在经历生理修饰的培养细胞中，或在降脂药物或乙醇的影响下，由其前体物质进行的生物合成过程。在神经母细胞瘤细胞SK-N-BE中，从亚油酸（LA，18:2 n-6）前体形成花生四烯酸（AA，20:4 n-6）的过程在分化早期增强，而在分化完成时下降，同时细胞脂质中AA的积累达到最大值。在单核细胞THP-1中，用HMGCoA还原酶抑制剂辛伐他汀（S）处理也会增强LC-PUFA的生物合成，甲羟戊酸和胆固醇合成的其他中间产物可逆转这种作用。S对LC-PUFA合成的最大激活作用发生在低于最大抑制胆固醇合成所需的浓度下。在肝癌细胞HepG2中，乙醇会降低LC-PUFA的生物合成，同时增强乙酸盐掺入胆固醇的过程。因此，从通过药理学操作获得的数据判断，LC-PUFA的合成似乎在细胞分化过程中受到调节，并且LC-PUFA与胆固醇合成之间发生了复杂的相互作用。
