COMPARATIVE CYTOTOXIC EFFECTS OF 2 PROTEIN PHOSPHATASE INHIBITORS, OKADAIC ACID AND CALYCULIN-A, ON THYROID-CELLS

The cytotoxicity of two inhibitors of protein phosphatases PP1 and PP2 A has been investigated on primary cultures of dog thyrocytes, Both co mpounds, okadaic acid and calyculin A elicited dose- and time- related effects, i.e. apoptosis and necrosis, In addition a pronounced detach ment of the cells from the monolayer was also observed, Based on the d ifferent patterns of morphological alterations and on the biochemical data, it was concluded that each compound induced different types of c ell death; this provides additional evidence that a specific cell type can initiate distinct programs of death depending on the triggering s timulus, To explain the effects recorded when both compounds were adde d concomitantly, a functional interaction between PP1 and PP2A has bee n proposed, Finally, all the effects appeared modulated, to different extent, by cycloheximide and by actinomycin D. This supports the view that de novo RNA synthesis is required for the induction of death by t hese phosphatase inhibitors in these cells.