calyculin-a and mevastatin

The effect of compactin (a lovastatin analogue) on vascular smooth muscle cells was studied at the level of cell proliferation and protein kinase C. It was observed: a) an inhibition of cell proliferation by compactin at a micromolar range, which was prevented by simultaneous addition of mevalonate; b) a stimulation of DNA synthesis with a shift in the cell cycle kinetics, either in the presence or absence of fetal calf serum and c) an increase in protein kinase C activity in compactin-treated cells in the G1 phase of the cycle. This increase was similar to the one elicited by calyculin A, an inhibitor of protein phosphatases of type PP-1 and PP-2A. It is suggested that compactin behaves as a PP-1/PP-2A protein phosphatase inhibitor, inhibiting proliferation of smooth muscle cells by a block of the cell cycle after the S-phase.

Topics: Animals; Cell Division; Cell Line; Enzyme Activation; Enzyme Inhibitors; Hypolipidemic Agents; Lovastatin; Marine Toxins; Mevalonic Acid; Muscle, Smooth, Vascular; Oxazoles; Phosphoprotein Phosphatases; Protein Kinase C; Rats