Derventzi A, Rattan S I, Clark B F
Department of Chemistry, Aarhus University, Denmark.
Biochem Int. 1992 Aug;27(5):903-11.
4-beta-phorbol-12-beta-myristate-13-alpha-acetate (PMA) alters cellular growth properties by modulating gene expression in a wide variety of cell types. Human diploid fibroblasts MRC-5 were treated with PMA at different phases of their lifespan in vitro and the alterations of their short-term growth characteristics and macromolecular synthesis in response to PMA were analysed. PMA stimulates DNA and RNA synthesis in both Phase II (young) and Phase III (senescent) MRC-5 cells. Treatment of senescent cells with various PMA concentrations results in a greater stimulation of DNA and RNA synthesis than that in young cells. Senescent cells are also more sensitive to the PMA-induced alterations of growth characteristics and higher concentrations of PMA become toxic for them. The age-related alterations of cellular responsiveness are also apparent in the gradual loss of responsiveness to serum, observed in parallel with the increased sensitivity to PMA. Furthermore, serum-induced stimulation of macromolecular synthesis is inhibited by PMA. Since it is known that serum and PMA elicit their effects via different signal transduction pathways, our results point to suggest the differential regulation of the signalling mechanisms during cellular ageing.
4-β-佛波醇-12-β-肉豆蔻酸酯-13-α-乙酸酯（PMA）通过调节多种细胞类型中的基因表达来改变细胞生长特性。人二倍体成纤维细胞MRC-5在体外生命周期的不同阶段用PMA处理，并分析其短期生长特性和大分子合成对PMA的反应变化。PMA刺激II期（年轻）和III期（衰老）MRC-5细胞中的DNA和RNA合成。用不同浓度的PMA处理衰老细胞比处理年轻细胞能更大程度地刺激DNA和RNA合成。衰老细胞对PMA诱导的生长特性变化也更敏感，更高浓度的PMA对它们有毒性。细胞反应性与年龄相关的变化在对血清反应性的逐渐丧失中也很明显，这与对PMA敏感性增加同时出现。此外，PMA抑制血清诱导的大分子合成。由于已知血清和PMA通过不同的信号转导途径发挥作用，我们的结果表明细胞衰老过程中信号机制存在差异调节。
