NADH dehydrogenase deficiency in an apoptosis-resistant mutant isolated from a human HL-60 leukemia cell line.
An apoptosis-resistant mutant (VC-33) was selected from HL-60 by alternating exposure to camptothecin and etoposide. VC-33 cells demonstrated resistance to apoptosis as induced not only by camptothecin and etoposide but by a variety of other agents as well, including 1-beta-D-arabinofuranosylcytosine, hydroxyurea, calcium ionophore (A23187), cycloheximide, and UV irradiation. In an effort to identify the mechanism of such apoptosis resistance, a mRNA differential display analysis was used. Among a total of 12 bands with reduced expression in VC-33 cells, 1 cDNA clone was isolated that was hybridized to the wild-type transcript but not to the VC-33 transcript on Northern blotting. Partial sequence of this gene revealed 98% homology to mitochondrial NADH dehydrogenase subunit 5. When cell growth and intracellular ATP levels under glucose starvation were measured, VC-33 cells were found to be more sensitive than wild-type cells. Thus, NADH dehydrogenase deficiency may contribute, at least in part, to the mechanism of resistance to apoptosis in VC-33 cells.
Kataoka
A
A
Department of Pediatrics, Faculty of Medicine, Kyoto University, Japan.
Kubota
M
M
Watanabe
K
K
Sawada
M
M
Koishi
S
S
Lin
Y W
YW
Usami
I
I
Akiyama
Y
Y
Kitoh
T
T
Furusho
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000001:Calcimycin / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003001:Cloning, Molecular; D003561:Cytarabine / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D046911:Macromolecular Substances; D008928:Mitochondria / Q000201:enzymology; D016296:Mutagenesis; D009245:NADH Dehydrogenase / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D046911:Macromolecular Substances; D003561:Cytarabine; D000001:Calcimycin; D005047:Etoposide; D003847:Deoxyglucose; D009245:NADH Dehydrogenase; D005947:Glucose; D006918:Hydroxyurea; D002166:Camptothecin