Does chloroquine, an antimalarial drug, affect autophagy in Tetrahymena pyriformis?
The effect of chloroquine (CQ) on autophagy was studied in starved Tetrahymena pyriformis. When a proliferating Tetrahymena culture is transferred to a starvation medium, autophagy commences although cells most advanced in the cell cycle will divide. The drug was added to 1-h starved cells at different pH values because CQ affects pH dependently. The CQ concentration blocking all cell divisions was determined as the lowest toxic, but sublethal, concentration. Hence, the highest tolerated concentrations at pH 6.8, 7.1, and 7.7 were 1.0, 0.3, and 0.03 mM CQ, respectively. Lower CQ concentrations had a dose-dependent effect on cell increment and higher concentrations induced cell mortality. Rates of cell motility and decreases in cell volume were affected by the drug, while the capacity for endocytosis was unaffected in low concentrations but affected dose dependently in high concentrations. Light microscopically, all drug-treated cells contained small refractive bodies, but in toxic concentrations they also contained conspicuously large vacuoles. After 1 h and 4 h in CQ, fine structure analysis showed autophagosomes with electron-dense material in cells in tolerated concentrations and of enlarged size, but decreased number, in toxic concentrations. The contents of autophagosomes revealed cell organelles in different stages of disintegration. The conclusion is that the drug enhances autophagy in Tetrahymena in a pH-, dose-, and time-dependent manner.
Nilsson
J R
JR
Institute of Cell Biology and Anatomy, University of Copenhagen, Denmark.
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002465:Cell Movement; D002738:Chloroquine / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D002738:Chloroquine