SELECTIVE-INHIBITION OF COLLAGEN-SYNTHESIS BY OKADAIC ACID IN CULTURED HUMAN FIBROBLASTS

To determine whether protein phosphatases can affect collagen synthesis, we examined the effect of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on collagen synthesis. Okadaic acid significantly decreased the [H-3]proline incorporation into the collagenase-digestible protein and the percent collagen synthesis. These effects were synergistic with phorbol myristate acetate (PMA). The time course study showed that okadaic acid inhibited collagen synthesis after a 12 h treatment while PMA inhibited at 3 h. Down-regulation of protein kinase C by chronic treatment with PMA did not abrogate the okadaic acid-dependent inhibition. These results provide evidence for the involvement of protein phosphatases in the regulation of collagen synthesis. (C) 1994 Academic Press, Inc.