Variable susceptibility to apoptosis induced by calcium ionophore in hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cell lines: relationship to constitutive Mg(2+)-dependent endonuclease.
We recently reported that treatment with calcium ionophore, A23187, induces apoptosis in human myelogenous leukemia cells but causes necrotic cell death in T-lymphoblastic leukemia cells. To better understand the underlying mechanisms of such different modes of cell death, we established hybridomas between HL-60 promyelocytic and CEM T-lymphoblastic leukemia cells. The resulting hybridomas were divided into three groups in terms of their susceptibility to apoptosis following exposure to A23187: (1) hybridomas highly sensitive to apoptosis, (2) hybridomas with intermediate sensitivity to apoptosis which occurs later and to a lesser extent, and (3) hybridomas resistant to apoptosis. However, growth inhibition after 72 h of incubation and an initial rise in intracellular free calcium concentrations induced by A23187 were similar in the three groups. Expression of Ca(2+)-independent/Mg(2+)-dependent endonuclease, which had an optimal pH of 7.5-8.5 and was inhibited by Zn2+, was correlated with the susceptibility of the hybridomas to A23187-induced apoptosis. Thus, this endonuclease may play, at least in part, an important role in the induction of apoptosis in leukemia cell lines. Analysis of hybridomas between apoptosis-sensitive and apoptosis-resistant cells is useful in the elucidation of genetic factors which regulate cell death.
Matsubara
K
K
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Kubota
M
M
Kuwakado
K
K
Hirota
H
H
Wakazono
Y
Y
Okuda
A
A
Bessho
R
R
Lin
Y W
YW
Adachi
S
S
Akiyama
Y
Y
D017209:Apoptosis; D000001:Calcimycin / Q000494:pharmacology*; D004720:Endonucleases / Q000378:metabolism; D006801:Humans; D006825:Hybridomas / Q000166:cytology* / Q000187:drug effects; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000001:Calcimycin; D004720:Endonucleases; D008274:Magnesium