ON THE MECHANISM OF ADAPTATION TO PROTEIN SYNTHESIS INHIBITORS BY TETRAHYMENA
Open Access
- 1 September 1974
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 62 (3), 707-716
- https://doi.org/10.1083/jcb.62.3.707
Abstract
Tetrahymena is able to adapt to the presence of sublethal concentrations of many drugs which inhibit a wide variety of cellular functions. In spite of the generality of this phenomenon in Tetrahymena, the mechanism of adaptation at the cellular and molecular levels is unknown. This study deals mainly with adaptation to the protein synthesis inhibitors, cycloheximide and emetine. The physiological response of Tetrahymena to sublethal concentrations of these drugs is an immediate cessation of cell division for a period of time dependent on the drug concentration, followed by an abrupt resumption of exponential growth at a constant rate. By measuring the length of the growth lags under a variety of experimental conditions, we have confirmed several observations made by Frankel and coworkers, and provide evidence for two new phenomena associated with adaptation to cycloheximide: (a) adaptation to cycloheximide also results in adaptation of cells to emetine, another protein synthesis inhibitor not closely related structurally to cycloheximide. We have termed this phenomenon cross adaptation, (b) exposure to concentrations of cycloheximide too low to cause any growth lags or inhibition of protein synthesis significantly shortens the time required by cells to adapt to higher concentrations of cycloheximide. We have termed this phenomenon facilitation. Facilitation shows some degree of specificity in that facilitation with cycloheximide has no effect on adaptation to emetine. From this, we infer the existence of two distinct systems involved in adaptation to cycloheximide, one of which shows a higher degree of specificity towards cycloheximide than the other. We also show that transfer of adapted or facilitated cells to drug-free medium results in a gradual but complete resensitization. The kinetics of resensitization suggest that the cellular machinery responsible for adaptation and facilitation does not leave the cell, but is simply diluted out during cell division.Keywords
This publication has 12 references indexed in Scilit:
- A cycloheximide-resistant mutant of Tetrahymena pyriformisExperimental Cell Research, 1973
- Inhibitors of protein synthesis in eukaryotes: tools in cell research.1973
- Transient inhibition by cycloheximide of protein synthesis in cultured plant cell suspensions: A dose response paradoxBiochemical and Biophysical Research Communications, 1973
- Protein synthesis in vitro with Tetrahymena mitochondrial ribosomesBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1972
- The kinetics of resensitization ofTetrahymena following recovery from effects of cycloheximideJournal of Cellular Physiology, 1971
- The Mechanism by which Cycloheximide and Related Glutarimide Antibiotics Inhibit Peptide Synthesis on Reticulocyte RibosomesJournal of Biological Chemistry, 1971
- An analysis of the recovery of Tetrahymena from effects of cycloheximideJournal of Cellular Physiology, 1970
- Inhibitors of protein biosynthesis. V. Effects of emetine on protein and nucleic acid biosynthesis in HeLa cells.1968
- STRUCTURAL BASIS FOR INHIBITION OF PROTEIN SYNTHESIS BY EMETINE AND CYCLOHEXIMIDE BASED ON AN ANALOGY BETWEEN IPECAC ALKALOIDS AND GLUTARIMIDE ANTIBIOTICSProceedings of the National Academy of Sciences, 1966
- The effect of nucleic acid antagonists on cell division and oral organelle development inTetrahymena pyriformisJournal of Experimental Zoology, 1965