[ ]-Stimulated Ion Fluxes Are Responsible for Apoptosis and Taxol Biosynthesis in Suspension Cultures of Taxus Cells

Ion fluxes across the plasma membrane activated by 1 mM $Ce^{4+}$, cell apoptosis and taxol biosynthesis in suspension cultures of Taxus cusp/data were studied. The extracellular pH sharply decreased upon the addition of 1 mM $Ce^{4+}$, then increased gradually and exceeded the initial pH value over a time period of 12 h. The extracellular $Ca^{2+}$ concentration decreased within the first 3 h after the addition of $Ce^{4+}$, then gradually decreased to one third of initial value in control at about 72 h and remained unchanged afterwards. Experiments with an ion channel blocker and a $Ca^{2+}$-channel blocker indicated that the dynamic changes in extracellular pH and the $Ca^{2+}$ concentration resulted from the $Ce^{4+}$-induced activation of W uptake and $Ca^{2+}$ influx across the plasma membrane via ion channels. A pretreatment of the ion channel blocker initiated $Ce^{4+}$-treated cells to undergo necrosis, and the prior addition of the $Ca^{2+}$-channel blocker inhibited $Ce^{4+}$-induced taxol biosynthesis and apoptosis. It is thus inferred that W uptake is necessary for cells to survive a $Ce^{4+}$-caused acidic environment and is one of the mechanisms of $Ce^{4+}$-induced apoptosis. Furthermore, the $Ca^{2+}$ influx across the plasma membrane mediated both the $Ce^{4+}$-induced apoptosis and taxol biosynthesis.