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Phosphatidylserine peroxidation/externalization during staurosporine‐induced apoptosis in HL‐60 cells
Author(s) -
Matsura Tatsuya,
Serinkan Behice F,
Jiang Jianfei,
Kagan Valerian E
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02990-3
Subject(s) - staurosporine , phosphatidylserine , apoptosis , oxidative stress , glutathione , cytosol , reactive oxygen species , microbiology and biotechnology , phagocytosis , cytochrome c , chemistry , lipid peroxidation , biochemistry , oxidative phosphorylation , biology , protein kinase c , signal transduction , phospholipid , enzyme , membrane
Although oxidative stress is commonly associated with apoptosis, its specific role in the execution of the apoptotic program has yet to be described. We hypothesized that catalytic redox interactions between negatively charged phosphatidylserine (PS) and positively charged cytochrome c released into the cytosol, along with the production of reactive oxygen species (ROS), results in pronounced oxidation and externalization of PS, and subsequent recognition of apoptotic cells by macrophages. By using staurosporine, a protein kinase inhibitor that does not act as a prooxidant, we were able to induce apoptosis in HL‐60 cells without triggering the confounding effects of non‐specific oxidation reactions. Through this approach, we demonstrated for the first time that PS underwent a statistically significant and pronounced oxidation at an early stage (2 h) of non‐oxidant‐induced apoptosis while the most abundant phospholipid, phosphatidylcholine, did not. Glutathione (GSH), the most abundant cytosolic thiol, also remained unoxidized at this time point. Furthermore, PS oxidation and the appearance of cytochrome c in the cytosol were concurrent; PS externalization was followed by phagocytosis of apoptotic cells. These findings are compatible with our proposed roles for oxidative PS‐dependent signaling during apoptosis and phagocytosis.