A study of the Influence of mevalonic acid and its metabolites on the morphology of swiss 3T3 cells.

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Abstract
Two model systems were used to investigate the effect of compactin, a competitive inhibitor of .beta.-hydroxy .beta.-methylglutarylcoenzyme a reductase, on the shape of Swiss 3T3 cells. Cells were maintained in a quiescent state in medium deficient in platelet-derived growth factor (PDGF), or PDGF was added to quiescent cells to initiate traverse through a single cell cycle. In both systems, the cells responded to compactin by acquiring a characteristic rounded shape. Cell rounding seemed to depend on an induced deficiency of mevalonic acid (MVA) since the response could be prevented or reversed by adding MVA to the culture medium. Compactin-induced rounding appeared in PDGF-stimulated cells concomitantly with a compactin-mediated inhibition of DNA synthesis, and both effects had similar sensitivities to exogenous compactin and MVA. However, cell rounding seemed to be unrelated to other, previously observed effects of MVA deficiency. Compactin did not influence the total content of cell cholesterol, and little cholesterol was formed when radioactive MVA was added to round cells to effect shape change reversal. Measurement of the dolichol-dependent glycosylation of cell protein revealed no evidence of dilichol deficiency. In addition, reversal of cell rounding by MVA was not prevented by concentrations of tunicamycin that effectively blocked the incorporation of radioactive mannose into cell protein or by concentrations of cycloheximide that blocked protein synthesis. A new role for MVA or its products in the maintenance of cell shape is suggested.

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