Effect of extracellular ATP on the human leukaemic cell line K562 and its multidrug counterpart.
Extracellular ATP (ATPo) is capable of inducing different events on cells through receptor activation. The effect produced by ATPo was studied in the cell line K562 and its multidrug resistant (MDR) counterpart, Lucena 1. Lower ATPo concentrations (1 mM and 2.5 mM) led to high (3)H-thymidine incorporation but no increase in cell number. Similarly, the cell cycle profile indicated an increase of cells in S phase and a decrease in G1 and G2, suggesting that the cells did not duplicate their DNA content. Higher doses of ATP (5 mM and 10 mM), as well as UTP (5 mM) and the P2X(7) agonist BzATP, were cytotoxic. However, no expression of P2X(7) receptors could be detected by Western Blot nor were the cells permeabilised by ATP, suggesting that pore formation was not involved in cell death. Both ecto-ATPase and ecto-5'-nucleotidase activity could be demonstrated at the surfaces of K562 and Lucena 1 cells, the latter presenting a higher ecto-5'-nucleotidase activity. Adenosine induced cell death at lower concentrations (2.5 mM) on both cell lines. Furthermore, an increased number of dead cells could be observed when 5 mM Adenosine was used compared to the same concentrations of ATPo. It still remains to be elucidated the nature of the receptors involved in the induction of cell death in these cells.
Bernardo
Alcira A
AA
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, RJ, Brazil.
Pinto-Silva
Flavio Eduardo
FE
Persechini
Pedro M
PM
Coutinho-Silva
Robson
R
Meyer-Fernandes
José Roberto
JR
de Souza
André Luiz Fonseca
AL
Rumjanek
Vivian M
VM
D015720:5'-Nucleotidase / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001081:Apyrase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D013936:Thymidine / Q000096:biosynthesis; D014316:Tritium; D014407:Tumor Cells, Cultured; D014544:Uridine Triphosphate / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C546468:P2RX7 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014316:Tritium; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001081:Apyrase; D000241:Adenosine; D014544:Uridine Triphosphate; D013936:Thymidine