Abstract
Phosphatidylserine (PS) externalization is a key feature of apoptotic cell death and plays an important role in clearance of apoptotic cells by phagocytes. PS externalization during apoptosis is generally an irreversible event mediated by caspase activation and is accompanied by other apoptotic events. We report here that an apoptosis inducer α-tocopheryl succinate (TOS) can induce PS externalization that is independent of apoptosis and reversible in the absence of fetal bovine serum (FBS) in histiocytic lymphoma U937 cells. In the presence of FBS, TOS induced PS externalization via a caspase-dependent mechanism accompanied by mitochondrial depolarization, cell shrinkage, increase of caspase-3 activity, and chromatin condensation. In contrast, in the absence of FBS, TOS induced the rapid PS externalization which was not accompanied by other apoptotic events. The PS externalization was reversible by removing TOS and was not involved in Ca2+-dependent scramblase activation and thiol oxidation of aminophospholipid translocase. A similar PS externalization was also induced by cholesteryl hemisuccinate (CS), the other succinate ester. These results suggested that the mechanism of TOS- and CS-induced PS externalization in the absence of FBS was different from it occurring during typical apoptosis.
| Original language | English |
|---|---|
| Pages (from-to) | 137-149 |
| Number of pages | 13 |
| Journal | Molecular and Cellular Biochemistry |
| Volume | 333 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jan 2010 |
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Keywords
- α-Tocopheryl succinate
- Aminophospholipid translocase
- Apoptosis
- Non-apoptosis
- Phosphatidylserine externalization
- Reversible
- Scramblase
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Cell Biology
Cite this
α-Tocopheryl succinate induces rapid and reversible phosphatidylserine externalization in histiocytic lymphoma through the caspase-independent pathway. / Fujita, Hirofumi; Shiva, Daisuke; Utsumi, Toshihiko; Ogino, Tetsuya; Ogawa, Tomohiro; Abe, Koichi; Yasuda, Tatsuji; Utsumi, Kozo; Sasaki, Junzo.
In: Molecular and Cellular Biochemistry, Vol. 333, No. 1-2, 01.2010, p. 137-149.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - α-Tocopheryl succinate induces rapid and reversible phosphatidylserine externalization in histiocytic lymphoma through the caspase-independent pathway
AU - Fujita, Hirofumi
AU - Shiva, Daisuke
AU - Utsumi, Toshihiko
AU - Ogino, Tetsuya
AU - Ogawa, Tomohiro
AU - Abe, Koichi
AU - Yasuda, Tatsuji
AU - Utsumi, Kozo
AU - Sasaki, Junzo
PY - 2010/1
Y1 - 2010/1
N2 - Phosphatidylserine (PS) externalization is a key feature of apoptotic cell death and plays an important role in clearance of apoptotic cells by phagocytes. PS externalization during apoptosis is generally an irreversible event mediated by caspase activation and is accompanied by other apoptotic events. We report here that an apoptosis inducer α-tocopheryl succinate (TOS) can induce PS externalization that is independent of apoptosis and reversible in the absence of fetal bovine serum (FBS) in histiocytic lymphoma U937 cells. In the presence of FBS, TOS induced PS externalization via a caspase-dependent mechanism accompanied by mitochondrial depolarization, cell shrinkage, increase of caspase-3 activity, and chromatin condensation. In contrast, in the absence of FBS, TOS induced the rapid PS externalization which was not accompanied by other apoptotic events. The PS externalization was reversible by removing TOS and was not involved in Ca2+-dependent scramblase activation and thiol oxidation of aminophospholipid translocase. A similar PS externalization was also induced by cholesteryl hemisuccinate (CS), the other succinate ester. These results suggested that the mechanism of TOS- and CS-induced PS externalization in the absence of FBS was different from it occurring during typical apoptosis.
AB - Phosphatidylserine (PS) externalization is a key feature of apoptotic cell death and plays an important role in clearance of apoptotic cells by phagocytes. PS externalization during apoptosis is generally an irreversible event mediated by caspase activation and is accompanied by other apoptotic events. We report here that an apoptosis inducer α-tocopheryl succinate (TOS) can induce PS externalization that is independent of apoptosis and reversible in the absence of fetal bovine serum (FBS) in histiocytic lymphoma U937 cells. In the presence of FBS, TOS induced PS externalization via a caspase-dependent mechanism accompanied by mitochondrial depolarization, cell shrinkage, increase of caspase-3 activity, and chromatin condensation. In contrast, in the absence of FBS, TOS induced the rapid PS externalization which was not accompanied by other apoptotic events. The PS externalization was reversible by removing TOS and was not involved in Ca2+-dependent scramblase activation and thiol oxidation of aminophospholipid translocase. A similar PS externalization was also induced by cholesteryl hemisuccinate (CS), the other succinate ester. These results suggested that the mechanism of TOS- and CS-induced PS externalization in the absence of FBS was different from it occurring during typical apoptosis.
KW - α-Tocopheryl succinate
KW - Aminophospholipid translocase
KW - Apoptosis
KW - Non-apoptosis
KW - Phosphatidylserine externalization
KW - Reversible
KW - Scramblase
UR - http://www.scopus.com/inward/record.url?scp=73449136837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73449136837&partnerID=8YFLogxK
U2 - 10.1007/s11010-009-0214-2
DO - 10.1007/s11010-009-0214-2
M3 - Article
C2 - 19633976
AN - SCOPUS:73449136837
VL - 333
SP - 137
EP - 149
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -