MICROCYSTIN-LR INDUCED AN INHIBITION OF PROTEIN-SYNTHESIS IN ISOLATEDRAT HEPATOCYTES

The effect of microcystin-LR, an inhibitor of protein phosphatases PP1 and PP2A, was studied on protein synthesis by measuring the incorpora tion of labelled amino acid into protein in isolated rat hepatocytes. Microcystin-LR inhibited protein synthesis in the first minutes of the incubation period, and half-maximum effect was obtained at about 60 n M. Such an inhibition was also observed in the presence of different p rotein phosphatase inhibitors, i.e. okadaic acid, calyculin A and micr ocystin-RR. This effect was observed in whole hepatocytes in the super natant of the post-mitochondrial fraction and in the microsomal fracti on. It was independent of a substrate supply and of the labelled amino acid used. Furthermore, this inhibition preceded the previously repor ted glucose-6-phosphatase activation induced by microcystin-LR [Claeys sens, Chedeville and Lavoinne (1993) FEBS Lett. 315, 7-10].