De Tata V, Ptasznik A, Cristofalo V J
Center for Gerontological Research, Medical College of Pennsylvania, Philadelphia 19129.
Exp Cell Res. 1993 Apr;205(2):261-9. doi: 10.1006/excr.1993.1085.
The effects of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on the proliferation, protein kinase C activity (PKC), and c-fos gene expression were examined in cultures of young and senescent (90-95% lifespan completed) WI-38 human diploid fibroblasts. We observed that, following stimulation with medium containing 10% fetal bovine serum (FBS), the translocation of PKC from the cytosol to the particulate compartment was less efficient in senescent WI-38 cells than in young cells. However, when PMA was added to the medium, the intracellular distribution of PKC activity in old cells became nearly identical to that observed in young cells. The inducibility of c-fos mRNA by serum addition, which is a protein kinase C-dependent event, was significantly amplified in the presence of PMA. Moreover, the duration of peak c-fos expression, after stimulation by FBS and PMA, increased in senescent cells as compared to young cells. Our results reveal that the normal signal transduction pathway is altered in senescent, slowly proliferating human fibroblasts and that it can be partially restored in the presence of the tumor promoter PMA.
在年轻和衰老（已完成90 - 95%寿命）的WI - 38人二倍体成纤维细胞培养物中，研究了肿瘤促进剂佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）对细胞增殖、蛋白激酶C活性（PKC）和c - fos基因表达的影响。我们观察到，在用含10%胎牛血清（FBS）的培养基刺激后，衰老的WI - 38细胞中PKC从胞质溶胶向颗粒区室的转位效率低于年轻细胞。然而，当向培养基中添加PMA时，老细胞中PKC活性的细胞内分布变得与年轻细胞中观察到的几乎相同。血清添加对c - fos mRNA的诱导作用（这是一个依赖蛋白激酶C的事件）在PMA存在下显著增强。此外，与年轻细胞相比，衰老细胞在FBS和PMA刺激后c - fos表达峰值的持续时间增加。我们的结果表明，正常的信号转导途径在衰老的、增殖缓慢的人成纤维细胞中发生了改变，并且在肿瘤促进剂PMA存在下它可以部分恢复。
