EXPOSURE TO ORNITHINE RESULTS IN EXCESSIVE ACCUMULATION OF PUTRESCINEAND APOPTOTIC CELL-DEATH IN ORNITHINE DECARBOXYLASE OVERPRODUCING MOUSE MYELOMA CELLS
Ke. Tobias et C. Kahana, EXPOSURE TO ORNITHINE RESULTS IN EXCESSIVE ACCUMULATION OF PUTRESCINEAND APOPTOTIC CELL-DEATH IN ORNITHINE DECARBOXYLASE OVERPRODUCING MOUSE MYELOMA CELLS, Cell growth & differentiation, 6(10), 1995, pp. 1279-1285
Ornithine decarboxylase (ODC) is the first key enzyme in the biosynthe
sis of polyamines, aliphatic polycations that are indispensable for th
e process of mammalian cell proliferation. The mouse myeloma cell line
, 653-1, massively overproduces ODC due to the amplification of an act
ive 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 oligon
ucleosome-sized DNA ''ladder''; consequently, their death can be descr
ibed as apoptosis. Accumulation of putrescine in 653-1 cells is accomp
anied by a rapid decrease of protein synthesis activity, suggesting th
at protein synthesis inhibition may be the cause for the apoptotic dea
th of 653-1 cells. However, since the apoptotic death provoked by expo
sure of 653-1 cells to ornithine reached a maximal level earlier than
that caused by cycloheximide, we conclude that protein synthesis inhib
ition is unlikely to be the direct cause of the observed apoptotic cel
l death.