Induction of apoptosis by excessive polyamine accumulation in ornithine decarboxylase-overproducing L1210 cells.
Deregulation of polyamine transport in L1210 cells overexpressing ornithine decarboxylase leads to a lethal accumulation of spermidine. We now provide evidence that over-accumulation of natural and synthetic polyamines, but not putrescine, rapidly induces apoptosis, as shown by hypercondensation of peripheral chromatin and internucleosomal cleavage, followed by nuclear fragmentation. Polyamine oxidation is not responsible for the apoptosis observed. Thus, abnormally high polyamine pools could be an important physiological trigger of apoptosis.
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015317:Biogenic Polyamines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D004273:DNA, Neoplasm / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007939:Leukemia L1210; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D009995:Osmosis; D010084:Oxidation-Reduction; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism
D015317:Biogenic Polyamines; D004273:DNA, Neoplasm; D006861:Hydrogen Peroxide; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine