Polyamine depletion switches the form of 2-deoxy-D-ribose-induced cell death from apoptosis to necrosis in HL-60 cells.
Our previous studies demonstrated that intracellular polyamine depletion blocked HL-60 cell apoptosis triggered by exposure to 2-deoxy-d-ribose (dRib). Here, we have characterized the intracellular events underlying the apoptotic effects of dRib and the involvement of polyamines in these effects. Treatment of HL-60 cells with dRib induces loss of mitochondrial transmembrane potential, radical oxygen species production, intracellular glutathione depletion and translocation of Bax from cytosol to membranes. These effects are followed by cell death. However, the mode of cell death caused by dRib depends on intracellular levels of polyamines. d-Rib-treated cells with normal polyamine levels, progressing through the G(1) into the S and G(2)/M phases, undergo apoptosis, while in polyamine-depleted cells, being blocked at the G(1) phase, cell death mechanisms are switched to necrosis. The present study points to a relationship between the cell cycle distribution and the mode of cell death, and suggests that the level of intracellular spermidine, essential to cell cycle progression, may determine whether a cell dies by apoptosis or necrosis in response to a death stimulus.
Monti
Maria Giuseppina
MG
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41100 Modena, Italy. monti.mariagiuseppina@unimo.it
Ghiaroni
Stefania
S
Marverti
Gaetano
G
Montanari
Monica
M
Moruzzi
Maria Stella
MS
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000648:ultrastructure; D004247:DNA / Q000032:analysis; D003855:Deoxyribose / Q000494:pharmacology / Q000633:toxicity*; D000518:Eflornithine / Q000494:pharmacology; D005434:Flow Cytometry; D005978:Glutathione / Q000032:analysis / Q000096:biosynthesis; D018922:HL-60 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress; D011073:Polyamines / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D003855:Deoxyribose; D004247:DNA; D005978:Glutathione; D000518:Eflornithine