Intracellular ATP is required for actinomycin D-induced apoptotic cell death in HeLa cells.
In the present report, we demonstrate that reduction of cellular ATP content with antimycin A blocks actinomycin D-induced apoptotic cell death in HeLa cells. Compared to cells (approximately 80%) treated with actinomycin D (1 microgram/ml; 48 h) alone in glucose-containing medium, a much smaller percentage of cells (approximately 20%) treated with actinomycin D in the presence of antimycin A in glucose-free medium shows morphological characteristic of apoptosis. ATP-depleted cells with or without actinomycin D treatment, on the other hand, die necrotically. In cells under actinomycin D short exposure treatment (1 microgram/ml; 1 h), apoptosis occurs when cellular ATP content is rapidly recovered after the removal of antimycin A and resupplementation of glucose-containing medium. In the incubation of isolated Triton-permeabilized cells with ATP ( > 0.5 mM), apoptotic nuclei become abundant 4 h after ATP treatment. These results implicate the requirement of ATP for the induction of apoptosis.
Chou
C C
CC
Graduate Institute of Pharmacology, Yang Ming Medical College, Taiwan, Republic of China.
Lam
C Y
CY
Yung
B Y
BY
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability; D002470:Cell Survival; D003470:Culture Media; D003609:Dactinomycin / Q000494:pharmacology*; D005947:Glucose; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D013997:Time Factors
D003470:Culture Media; D003609:Dactinomycin; D000255:Adenosine Triphosphate; D005947:Glucose