Exposure to ornithine results in excessive accumulation of putrescine and apoptotic cell death in ornithine decarboxylase overproducing mouse myeloma cells.
Ornithine decarboxylase (ODC) is the first key enzyme in the biosynthesis of polyamines, aliphatic polycations that are indispensable for the process of mammalian cell proliferation. The mouse myeloma cell line, 653-1, massively overproduces ODC due to the amplification of an active ODC gene. The addition of ornithine to the growth medium of 653-1 cells results in a massive increase in the intracellular concentration of putrescine, followed by rapid cell death. Ornithine-treated 653-1 cells display fragmented nuclei, chromatin condensation, and an oligonucleosome-sized DNA "ladder"; consequently, their death can be described as apoptosis. Accumulation of putrescine in 653-1 cells is accompanied by a rapid decrease of protein synthesis activity, suggesting that protein synthesis inhibition may be the cause for the apoptotic death of 653-1 cells. However, since the apoptotic death provoked by exposure of 653-1 cells to ornithine reached a maximal level earlier than that caused by cycloheximide, we conclude that protein synthesis inhibition is unlikely to be the direct cause of the observed apoptotic cell death.
Tobias
K E
KE
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Kahana
C
C
D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015317:Biogenic Polyamines / Q000096:biosynthesis; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008623:Mercaptoethanol / Q000494:pharmacology; D051379:Mice; D009101:Multiple Myeloma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009952:Ornithine / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011700:Putrescine / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; D004791:Enzyme Inhibitors; D006146:Guanidines; D011500:Protein Synthesis Inhibitors; D008623:Mercaptoethanol; D004247:DNA; D003513:Cycloheximide; D009952:Ornithine; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D009955:Ornithine Decarboxylase; C004479:pimagedine; D011700:Putrescine