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J. Biochem, 1998, Vol. 123, No. 6 1073-1078
© 1998 Japanese Biochemical Society

research-article

Induction of Apoptosis by Phosphatidylserine

Kayoko Uchida*,1, Kazuo Emoto*, David L. Daleke{ddagger}, Keizo Inoue{dagger} and Masato Umeda*,1

*Department of Inflammation Research, The Tokyo Metropolitan Institute of Medical Science (RINSHOKEN) 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613
{dagger}Department of Health Chemistry, Faculty of Pharmaceutical Science, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654
{ddagger}Department of Biochemistry and Molecular Biology, Indiana University Bloomington, IN47405, USA

1To whom correspondence should be addressed. Tel: +81-3-3823-2101 (Ext. 5419), Fax: +81-3-3823-2130, E-mail: umeda{at}rinshoken.or.jp

Treatment of Chinese hamster ovary (CHO) cells with phosphatidylserine (PS) caused cell death in a dose-dependent manner. Other phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid, had no effect on cell viability. The cells incubated with PS became round and underwent a dramatic reduction of cellular volume while maintaining the membrane containment of cellular contents. The PS-treatment induced chromatin condensation and extensive DNA fragmentation, with a pattern characteristic of internucleosomal fragmentation on agarose gel electrophoresis. These results indicate that PS-treatment induces apoptosis of CHO cells. This apoptosis-inducing activity was highly specific for PS, and neither of the synthetic PS analogs 1,2-diacyl-sn-glycero-3-phospho-D-serine (D-PS) and 2,3-diacyl-sn-glycero-1-phospho-L-serine induced apoptosis. Analysis using fluorescence-labeled phospholipids showed that both PS and D-PS were taken up equally and then transported to intracellular membranes, suggesting that the PS-specific induction of apoptosis was not the result of its specific internalization. These observations suggest that certain molecules which may recognize the stereo-specific configuration of PS are involved in the apoptotic process triggered by PS.


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