Biochemical and Biophysical Research Communications. 2006 Mar 29; [Epub ahead of print] [Link]
Jiri Neuzila, b, Lan-Feng Donga, Xiu-Fang Wanga and Jean-Marc Zinggc
aApoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia
bLaboratory of Cell Signalling and Apoptosis, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
cInstitute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
Received 7 March 2006. Available online 20 March 2006.
alpha-Tocopheryl succinate (alpha-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 alpha-TOS in malignant mesothelioma (MM) cells. Over-expression of TAP1 in MM cells sensitised them to apoptosis by low doses of alpha-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 alpha-TOS for TAP1. Finally, TAP1 over-expressing cells accumulated alpha-TOS at higher levels compared to their normal counterparts. We suggest that TAP1 may act as an intracellular shuttle for alpha-TOS, promoting apoptosis initiated by this vitamin E analogue, as shown here for MM cells.