Nitric oxide induces apoptosis in NALM-6, a leukaemia cell line with low cyclin E protein levels.
Intracellular nitric oxide levels may differ in resting and stimulated cells and contribute to the regulation of cell survival and proliferation through a variety of mechanisms and effects. We exposed two B-cell lines to a range of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) concentrations in order to examine their susceptibility to exogenous nitric oxide and the participation of nitric oxide as modulator of cell proliferation. Although both FLEB and NALM-6 decreased their levels of thymidine incorporation, only NALM-6 cells were induced to undergo G1 arrest, phosphatidyl serine exposure and DNA fragmentation when cultured in the presence of 250 microm SNAP. This higher sensitivity of NALM-6 coincided with initially low cyclin E protein levels which were increased 7.8-fold after culture for 24 h with 250 microm SNAP. In contrast, there was no difference in cyclins A and D3, Bcl-2 and actin levels, neither at the beginning nor at the end of the 24 h culture. Our study reveals that FLEB and NALM-6 exhibit different response to the same concentration of nitric oxide, that nitric oxide can simultaneously induce cell cycle alterations and apoptosis, and further suggests an association between these two processes, with the involvement of cell cycle regulatory molecules.
Mozart
M
M
Department of Haematology, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Scuderi
R
R
Celsing
F
F
Aguilar-Santelises
M
M
D000199:Actins / Q000096:biosynthesis; D017209:Apoptosis; D001402:B-Lymphocytes / Q000473:pathology; D015153:Blotting, Western; D002453:Cell Cycle; D002469:Cell Separation; D019925:Cyclin A / Q000096:biosynthesis; D056743:Cyclin D3; D019927:Cyclin E / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis; D053938:DNA Fragmentation; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000199:Actins; D019925:Cyclin A; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D010396:Penicillamine; D013936:Thymidine