Phosphatidylserine Externalization Is a Downstream Event of Interleukin-1β–Converting Enzyme Family Protease Activation During Apoptosis

作者：Mikihiko Naito, Kimie Nagashima, Tetsuo Mashima, Takashi Tsuruo · 发表于：Blood · 年份：1997 · DOI：10.1182/blood.v89.6.2060 · 被引用次数：132 · 研究领域：Phagocytosis and Immune Regulation、Cell death mechanisms and regulation、Protein Kinase Regulation and GTPase Signaling

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.