Induction of apoptosis by phosphatidylserine

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.