Comparative cytotoxic effects of two protein phosphatase inhibitors, okadaic acid and calyculin A, on thyroid cells.
The cytotoxicity of two inhibitors of protein phosphatases PP1 and PP2A has been investigated on primary cultures of dog thyrocytes. Both compounds, okadaic acid and calyculin A elicited dose- and time- related effects, i.e. apoptosis and necrosis. In addition a pronounced detachment of the cells from the monolayer was also observed. Based on the different patterns of morphological alterations and on the biochemical data, it was concluded that each compound induced different types of cell death; this provides additional evidence that a specific cell type can initiate distinct programs of death depending on the triggering stimulus. To explain the effects recorded when both compounds were added concomitantly, a functional interaction between PP1 and PP2A has been 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 these phosphatase inhibitors in these cells.
Golstein
J
J
I.R.I.B.H.N- ULB, Campus Erasme, Brussels, Belgium.
Swillens
S
S
Dumont
J E
JE