α-Tocopheryl succinate induces rapid and reversible phosphatidylserine externalization in histiocytic lymphoma through the caspase-independent pathway

Hirofumi Fujita, Daisuke Shiva, Toshihiko Utsumi, Tetsuya Ogino, Tomohiro Ogawa, Koichi Abe, Tatsuji Yasuda, Kozo Utsumi, Junzo Sasaki

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)137-149
Number of pages13
JournalMolecular and Cellular Biochemistry
Volume333
Issue number1-2
DOIs
Publication statusPublished - Jan 1 2010

Keywords

  • Aminophospholipid translocase
  • Apoptosis
  • Non-apoptosis
  • Phosphatidylserine externalization
  • Reversible
  • Scramblase
  • α-Tocopheryl succinate

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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