M. Naito et al., PHOSPHATIDYLSERINE EXTERNALIZATION IS A DOWNSTREAM EVENT OF INTERLEUKIN-1-BETA-CONVERTING ENZYME FAMILY PROTEASE ACTIVATION DURING APOPTOSIS, Blood, 89(6), 1997, pp. 2060-2066
Phosphatidylserine (PS), a class of acidic phospholipids, normally loc
alizes on the internal surface of cellular plasma membranes, The inter
nal PS is externalized when cells undergo apoptosis; however, the mech
anism for this is largely unknown. To study the mechanism of PS extern
alization during development of apoptosis, we examined the correlation
between the activation of interleukin-1 beta-converting enzyme (ICE)
family protease and PS externalization in human monocytic leukemia U93
7 cells and in their apoptosis-resistant variants, UK711 and UK110, af
ter treatment with etoposide and anti-fas antibody, We found that PS e
xternalization accompanied the development of apoptosis and the activa
tion of ICE family proteases in these cell lines, Furthermore, inhibit
ors of ICE family proteases, Z-Asp and Z-VAD, prevented apoptosis and
PS externalization in etoposide-treated U937 cells, These results indi
cate that PS externalization is a downstream event of ICE family prote
ase activation during apoptosis development, Because ICE family protea
ses play a crucial role in apoptosis, PS externalization could be a ra
tional and useful marker for the development of apoptosis. (C) 1997 by
The American Society of Hematology.