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(Received for publication, April 8, 1996, and in revised form, April 24, 1996)
From the We have investigated the cell death of a
Chinese hamster ovary mutant (MT-58) with a thermo-sensitive
CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of
the CDP-choline pathway for phosphatidylcholine biosynthesis (Esko, J. D., Wermuth, M. M., and Raetz, C. R. H. (1981) J. Biol.
Chem. 256, 7388-7393). After MT-58 cells were shifted to the
restrictive temperature of 40° C, the cytidylyltransferase was
inactivated immediately leading to a decrease in phosphatidylcholine
biosynthesis and cell death. DNA content and number of cells in the S
phase decreased significantly in the dying MT-58 cells according to
flow cytometrical analyses. The fragmentation of genomic DNA was
detected by DNA ladders in agarose gel and release of the prelabeled
genomic DNA into cytosolic fractions 14 h after the temperature
shift. The dying cells underwent a dramatic reduction of cellular
volume while maintaining the membrane containment of cellular contents.
These events indicated that the inactivation of cytidylyltransferase
triggered apoptosis in Chinese hamster ovary cells. This is the first
report that apoptosis was induced in cultured cells, not by an added
agent, but by a mutation in phospholipid biosynthesis.
Volume 271, Number 25,
Issue of June 21, 1996
pp. 14668-14671
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
COMMUNICATION:
,
,
,
,
and
Lipid and Lipoprotein Research
Group and Department of Biochemistry, ¶ Surgical-Medical Research
Institute, University of Alberta, Edmonton, Alberta T6G 2S2, Canada and
the
INSERM Unité 326, Hôpital Purpan, 31059
Toulouse cedex, France
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