Yeh W C, Bierer B E, McKnight S L
Johns Hopkins University, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11086-90. doi: 10.1073/pnas.92.24.11086.
Differentiating 3T3-L1 cells express an immunophilin early during the adipocyte conversion program as described in this issue [Yeh, W.-C., Li, T.-K., Bierer, B. E. & McKnight, S. L. (1995) Proc. Natl. Acad. Sci. USA 92, 11081-11085]. The temporal expression profile of this protein, designated FK506-binding protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones. Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs--cyclosporin A, FK506, and rapamycin--on the terminal-differentiation process. Adipocyte conversion was not affected by either cyclosporin A or FK506 and yet was significantly reduced by rapamycin at drug concentrations as low as 10 nM. Clonal expansion was impeded in drug-treated cultures, as was the accumulation of cytoplasmic lipid droplets normally seen late during differentiation. Rapamycin treatment likewise inhibited the expression of CCAAT/enhancer binding protein alpha, a transcription factor required for 3T3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory event was mediated by an immunophilin-rapamycin complex.
如本期所述[叶，W.-C.，李，T.-K.，比勒，B. E.和麦克奈特，S. L.（1995年）《美国国家科学院院刊》92，11081 - 11085]，分化中的3T3 - L1细胞在脂肪细胞转化程序早期表达一种亲免蛋白。这种名为FK506结合蛋白（FKBP）51的蛋白质的时间表达谱与3T3 - L1细胞在接触脂肪生成激素后进行的克隆扩增期一致。在观察到脂肪生成早期FKBP51的合成后，我们测试了三种免疫抑制药物——环孢素A、FK506和雷帕霉素——对终末分化过程的影响。脂肪细胞转化不受环孢素A或FK506的影响，但在低至10 nM的药物浓度下，雷帕霉素可使其显著降低。在药物处理的培养物中，克隆扩增受到阻碍，分化后期通常可见的细胞质脂滴积累也受到阻碍。雷帕霉素处理同样抑制了CCAAT/增强子结合蛋白α的表达，这是3T3 - L1细胞分化所需的一种转录因子。所有这三种效应都被高浓度的FK506逆转，表明起作用的抑制事件是由亲免蛋白 - 雷帕霉素复合物介导的。
