Tocopherol-associated protein-1 accelerates apoptosis induced by α-tocopheryl succinate in mesothelioma cells

Jiri Neuzil, Lan Feng Dong, Xiu Fang Wang, Jean Marc Zingg

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

α-Tocopheryl succinate (α-TOS), a redox-silent analogue of vitamin E, induces apoptosis in multiple cell lines in a selective manner, by activating the intrinsic pathway. Since it is a highly hydrophobic compound, it may require a carrier protein for its trafficking to intracellular targets like mitochondria. We studied the role of the ubiquitous tocopherol-associated protein-1 (TAP1 or sec14-like 2) in apoptosis induction by α-TOS in malignant mesothelioma (MM) cells. Over-expression of TAP1 in MM cells sensitised them to apoptosis by low doses of α-TOS which were sub-apoptotic for the parental cells. Apoptosis induced in TAP1-over-expressing cells was mitochondria- and caspase-dependent, as suggested by dissipation of mitochondrial trans-membrane potential and inhibition by zVAD-fmk, respectively. Binding assays showed affinity of α-TOS for TAP1. Finally, TAP1 over-expressing cells accumulated α-TOS at higher levels compared to their normal counterparts. We suggest that TAP1 may act as an intracellular shuttle for α-TOS, promoting apoptosis initiated by this vitamin E analogue, as shown here for MM cells.

Original languageEnglish (US)
Pages (from-to)1113-1117
Number of pages5
JournalBiochemical and biophysical research communications
Volume343
Issue number4
DOIs
StatePublished - May 19 2006
Externally publishedYes

Keywords

  • α-Tocopheryl succinate
  • Apoptosis
  • Malignant mesothelioma
  • Tocopherol-associated protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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