叶酸受体基因转染细胞诱导后的类脂改变对叶酸摄取的影响

Effects of Induced Lipoid Changes on the Folate Uptake by Transgenic Cells Expressing GPI anchored Folate Receptor

用胆固醇合成抑制剂Ｌｏｖａｓｔａｔｉｎ（洛伐他汀，暂译名）和神经鞘脂类合成抑制剂ＦｕｍｏｎｉｓｉｎＢ１（抑鞘脂素Ｂ１，暂译名）处理能表达糖基化磷脂酰肌醇锚定叶酸受体（ＧＰＩＦＲ）的基因转染细胞（ＦＲα·ＴＲＶＢ－１）３ｄ，发现前者可使细胞的胆固醇含量减少约３５％，而后者可使神经鞘脂类减少４４％以上；同时发现，处理组细胞结合叶酸的能力减少约４０％，其对５－甲基四氢叶酸的摄入率减少逾８０％．这主要是由于细胞质膜中胆固醇和神经鞘脂类含量减少，从而导致膜内ＧＰＩＦＲ结合叶酸功能降低及ＧＰＩＦＲ摄入叶酸的内化过程障碍所致．

To investigate the effects of changes in the cellular levels of sphingolipids and cholesterol on the folate uptake by the glycosylphosphatidylinositol anchored folate receptor(GPIFR),the FRα·TRVB 1 cells expressing GPIFR after gene transfection were used in model experiment.The cells were treated for 3 days with the lovastatin which inhibited biosynthesis of cholesterol and Fumonisin B 1 which inhibited biosynthesis of sphingolipids respectively.The results showed that cholesterol and the sphingolipids were reduced nearly 35% and over 40%,respectively as compared with the control.In addition,their cellular folic acid binding capacity lost approximately 40% and the folate receptor mediated transport of 5 methyl tetrahydro folate was blocked over 80% in the two treated groups.These data suggest that the depletion of cholesterol and sphingolipids on membrane of the treated cells may disrupt the clustering of the GPIFR and thus inhibit the cellular folate uptake by internalization.The involved mechanism of action needs further clarification.