Vannini F, Meacci E, Vasta V, Farnararo M, Bruni P
Department of Biochemical Sciences, University of Florence, Italy.
Mech Ageing Dev. 1994 Oct 20;76(2-3):101-11. doi: 10.1016/0047-6374(94)91585-7.
The proliferative response of IMR-90 fibroblasts at low and high population doubling level (PDL) to protein kinase C activation has been investigated to clarify whether the reduced mitogenic responsiveness of senescent cells can be ascribed to an alteration in protein kinase C signal transduction pathway. The results show that the signaling pathway leading to DNA synthesis through protein kinase C activation, appears to be modified in senescent IMR-90 human fibroblasts. High PDL fibroblasts exhibit a different sensitivity to phorbol 12-myristate 13-acetate (PMA) and dioctanoylglycerol (diC8); high glucose reduced responsiveness to PMA only in these cells. In addition, high PDL fibroblasts are characterized by an increase in diacylglycerol (DAG) cellular mass that could contribute to the different regulatory properties of the signaling pathway. On the other hand, the ability of the cyclooxygenase inhibitor indomethacin to strikingly improve the proliferative response of high PDL cells to PMA indicates that an altered overall metabolism of arachidonate may represent a crucial step in the reduced mitogenic response involving protein kinase C activation.
为了阐明衰老细胞有丝分裂反应性降低是否可归因于蛋白激酶C信号转导途径的改变，研究了处于低群体倍增水平（PDL）和高群体倍增水平的IMR-90成纤维细胞对蛋白激酶C激活的增殖反应。结果表明，在衰老的IMR-90人成纤维细胞中，通过蛋白激酶C激活导致DNA合成的信号转导途径似乎发生了改变。高PDL成纤维细胞对佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）和二辛酰甘油（diC8）表现出不同的敏感性；高糖仅在这些细胞中降低了对PMA的反应性。此外，高PDL成纤维细胞的特征是二酰基甘油（DAG）细胞质量增加，这可能导致信号转导途径的不同调节特性。另一方面，环氧化酶抑制剂吲哚美辛显著改善高PDL细胞对PMA增殖反应的能力表明，花生四烯酸整体代谢的改变可能是涉及蛋白激酶C激活的有丝分裂反应降低的关键步骤。
