Function of mevalonate in tobacco cell proliferation

We have used mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl- CoA reductase, to study the importance of mevalonic acid (MVA) for cell cycle progression of tobacco (Nicotiana tabacum L.) BY-2 (TBY-2) cells. Previously we have shown that in principal mevinolin blocks cells mainly at the end of G1 phase, but that cells are sensitive towards the inhibitor at the end of mitosis/entry G1 phase (Hemmerlin & Bach, 1998). The mevinolin—induced cell-cycle arrest was reversed by addition of exogenous MVA. It is shown that blockage of MVA synthesis might lead to variations in intracellular pH, which could be involved in the regulation of cell proliferation. SDS—PAGE analyses of total proteins and GTP—blot analyses indicate mevinolin—induced changes in the pattern, which can be reversed by addition of MVA. In preliminary experiments it has been demonstrated that artificial increase of the cytosolic pH partially released mevinolin—treated cells from the arrest in late G1 phase. A model is presented of ho...