Zhu W H, Loh T T
Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Biochem Pharmacol. 1996 May 3;51(9):1229-36. doi: 10.1016/0006-2952(96)00096-2.
The role of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) in apoptosis of HL-60 cells was investigated. PMA inhibited DNA fragmentation induced by thapsigargin (TG) and 4-bromo-calcium ionophore (Br-A23187). The inhibitory effect of PMA was concentration-related and was abolished by a specific PKC inhibitor, bisindolylmaleimide (GF109203X. In addition TG-induced apoptosis was decreased in cells in which PKC activity was down-regulated by long-term pretreatment with PMA. These results indicate that PKC activation by PMA inhibits HL-60 cell apoptosis induced by TG and Br-A23187, and that this inhibition is not influenced by the down-regulation of PKC. However, PMA did not inhibit DNA fragmentation induced by 1-beta-D-arabinofuranosylcytosine (Ara-C) and cycloheximide. PMA suppressed TG- or Br-A23187. Our results indicate that PKC participates in the regulation of apoptosis only by some pathways. Down-regulation of PKC is not responsible for the diverse effects of PKC activators on apoptosis. The effect of a PKC modulator on apoptosis is dependent upon interaction with individual apoptotic stimulus.
研究了蛋白激酶C（PKC）激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）在HL-60细胞凋亡中的作用。PMA抑制了毒胡萝卜素（TG）和4-溴钙离子载体（Br-A23187）诱导的DNA片段化。PMA的抑制作用呈浓度依赖性，且被特异性PKC抑制剂双吲哚马来酰胺（GF109203X）消除。此外，在通过长期用PMA预处理使PKC活性下调的细胞中，TG诱导的凋亡减少。这些结果表明，PMA激活PKC可抑制TG和Br-A23187诱导的HL-60细胞凋亡，且这种抑制不受PKC下调的影响。然而，PMA并不抑制1-β-D-阿拉伯呋喃糖基胞嘧啶（Ara-C）和环己酰亚胺诱导的DNA片段化。PMA抑制了TG或Br-A23187。我们的结果表明，PKC仅通过某些途径参与凋亡的调节。PKC的下调并非PKC激活剂对凋亡产生不同影响的原因。PKC调节剂对凋亡的影响取决于与个体凋亡刺激的相互作用。
