Phosphatidylserine externalization is a downstream event of interleukin-1 beta-converting enzyme family protease activation during apoptosis.
Phosphatidylserine (PS), a class of acidic phospholipids, normally localizes on the internal surface of cellular plasma membranes. The internal PS is externalized when cells undergo apoptosis; however, the mechanism for this is largely unknown. To study the mechanism of PS externalization 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 U937 cells and in their apoptosis-resistant variants, UK711 and UK110, after treatment with etoposide and anti-Fas antibody. We found that PS externalization accompanied the development of apoptosis and the activation of ICE family proteases in these cell lines. Furthermore, inhibitors of ICE family proteases, Z-Asp and Z-VAD, prevented apoptosis and PS externalization in etoposide-treated U937 cells. These results indicate that PS externalization is a downstream event of ICE family protease activation during apoptosis development. Because ICE family proteases play a crucial role in apoptosis, PS externalization could be a rational and useful marker for the development of apoptosis.
Naito
M
M
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Nagashima
K
K
Mashima
T
T
Tsuruo
T
T
D017209:Apoptosis; D020170:Caspase 1; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000201:enzymology; D010718:Phosphatidylserines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D007375:Interleukin-1; D010718:Phosphatidylserines; D003546:Cysteine Endopeptidases; D020170:Caspase 1