Okadaic acid promotes cell division in synchronized Tetrahymena pyriformis and in the cell division-arrested (cdaA1) temperature-sensitive mutant of T. thermophila.
1. Okadaic acid (OA) at 0.5 to 1 microM accelerated the onset and completion of division in heat-synchronized Tetrahymena pyriformis, especially where cells had been transiently delayed in the presence of dimethyl sulfoxide (DMSO). 2. The cell division-arrested mutant, cdaA1, of Tetrahymena thermophila ceased dividing after being shifted from the permissive temperature of 22 degrees C to the restrictive temperature of 37 degrees C, but continued to grow without forming fission furrows, resulting in deformed "monsters". In the presence of 1 microM OA, monster formation was completely inhibited, and over 20% of the mutant cells at 37 degrees C proceeded through a further apparently normal division. Evidence is presented for the first time that the potent and relatively selective PP2A inhibitor, okadaic acid (OA) can promote the entry and completion of Tetrahymena cell division as opposed to simply aiding the premature appearance of M-phase events seen in other cell systems. In this regard, the differential response to the combined action of OA and the kinase inhibitor 6-dimethyl-aminopurine (6-DMAP) at chosen stages of the cell cycle is shown. At early division, inhibitory effects of 6-DMAP were enhanced by the presence of OA, whereas in advanced stages of division, OA treatment by-passed 6-DMAP-induced inhibition and accelerated cells through division. The results are discussed in terms of the actions of these drugs on phosphorylation/dephosphorylation events responsible for driving division.
Buzanska
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Cell Pathology Laboratory, University Medical School, Aberdeen, Scotland/United Kingdom.
Wheatley
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DN
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D009154:Mutation; D019319:Okadaic Acid; D013696:Temperature; D013769:Tetrahymena pyriformis / Q000166:cytology* / Q000235:genetics; D016808:Tetrahymena thermophila / Q000166:cytology* / Q000235:genetics*; D013997:Time Factors
D004988:Ethers, Cyclic; D019319:Okadaic Acid; C001020:N(6),N(6)-dimethyladenine; D000225:Adenine; D004121:Dimethyl Sulfoxide