Voziyan P A, Goldner C M, Melnykovych G
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City 66103.
Biochem J. 1993 Nov 1;295 ( Pt 3)(Pt 3):757-62. doi: 10.1042/bj2950757.
The mechanism of inhibition of phosphatidylcholine (PC) biosynthesis by the isoprenoid farnesol was investigated in the human leukaemic CEM-C1 cell line. Cells were preincubated with 20 microM farnesol for up to 2 h and pulsed with [3H]choline. PC biosynthesis was inhibited to one-quarter at the step catalysed by cholinephosphotransferase (CPT). CPT activity in cellular homogenates from farnesol-treated cells was significantly decreased, but no changes in cytidylyltransferase activity or diacylglycerol concentration were observed. Measurements of CPT activity in the experiments in which farnesol was added directly to the homogenates or microsomal fractions demonstrated that farnesol did not affect CPT activity. However, cytosol from farnesol-treated samples decreased microsomal CPT activity almost twice as much as did cytosol from controls. This effect was found to be heat-stable, and disappeared after dialysis, but could not be attributed to farnesol present in the cytosol. The effect of farnesol was specific when compared with other structurally similar isoprenoids. We conclude that farnesol brings about changes in cultured cells, leading to decreased CPT activity, and thus to the inhibition of PC biosynthesis.
在人白血病CEM-C1细胞系中研究了类异戊二烯法尼醇抑制磷脂酰胆碱（PC）生物合成的机制。细胞先用20微摩尔法尼醇预孵育长达2小时，然后用[3H]胆碱脉冲处理。在胆碱磷酸转移酶（CPT）催化的步骤中，PC生物合成被抑制到四分之一。法尼醇处理的细胞的细胞匀浆中的CPT活性显著降低，但未观察到胞苷酰转移酶活性或二酰基甘油浓度的变化。在将法尼醇直接添加到匀浆或微粒体组分的实验中对CPT活性的测量表明，法尼醇不影响CPT活性。然而，法尼醇处理样品的胞质溶胶使微粒体CPT活性降低的程度几乎是对照胞质溶胶的两倍。发现这种作用是热稳定的，透析后消失，但不能归因于胞质溶胶中存在的法尼醇。与其他结构相似的类异戊二烯相比，法尼醇的作用具有特异性。我们得出结论，法尼醇导致培养细胞发生变化，导致CPT活性降低，从而抑制PC生物合成。
