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

Neuzil, Jiri; Dong, Lan-Feng; Wang, Xiu-Fang; Zingg, Jean-Marc (2006). Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells. Biochemical and biophysical research communications, 343(4), pp. 1113-7. Orlando, Fla.: Academic Press 10.1016/j.bbrc.2006.03.052

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Zingg, Jean-Marc

ISSN:

0006-291X

ISBN:

16579965

Publisher:

Academic Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:49

Last Modified:

05 Dec 2022 14:15

Publisher DOI:

10.1016/j.bbrc.2006.03.052

PubMed ID:

16579965

Web of Science ID:

000237269000018

URI:

https://boris.unibe.ch/id/eprint/20377 (FactScience: 3665)

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