The role of protein kinase C signal transduction pathways in the changes of both cell cycle and apoptosis of human embryonic pulmonary fibrob last induced by chrysotile

Abstract

Objective To explore the relationship betwe en protein kinase C(PKC) signal transduction pathway and the changes of both cel l cycle and apoptosis of human embryonic pulmonary fibroblast(HEPF) induced by chrysotile. Methods Flow cytometry to measure changes of both cell c ycle and apoptosis of HEPF induced by the supernatants of chrysotile-treated ra bbit alveolar macrophage(AM) was used,and different controls:blank control,norma l control(AM),negative (TiO2) and positive(SiO2) control were set up. Results In the process of proliferation of HEPF stimulated by the supernata nt of AM treated by chrysotile,the percentage of the cells of G2/M phase of HE PF in chrysotile group was 7.2%,higher than that in all controls;and the apoptos is percentage was 3.5%,significantly lower than that in all controls(P <0.01).PKC inhibitor(C25H24N4O2) made the percentage of cells of S phase decreased from 37.8% to 27.3%(P<0.01) and apoptosis perc entage increased from 3.5% to 22.7%(P<0.01),but PKC activator(PMA) made the percentage of S phase cells increased. Conclusion Th e change of cell cycle in HEPF proliferation induced by chrysotile was related t o the up-stream PKC signal pathway. The role of PKC activator or inhibitor was realized by p rimarily regulating DNA synthesis during S phase and inducing apoptosis of cell.