The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition

John G. Pastorino, Sing Tsung Chen, Marco Tafani, Jack W. Snyder, John L. Farber

Research output: Contribution to journalArticle

Abstract

Stably transfected Jurkat T cells were produced in which Bax expression is inducible by muristerone A. The cell death resulting from induction of the overexpresion of Bax was prevented by inhibition of the mitochondrial permeability transition (MPT) with cyclosporin A (CyA) in combination with the phospholipase A2 inhibitor aristolochic acid (ArA). The caspase-3 inhibitor Z-Asp-Glu-Val aspartic acid fluoromethylketone (Z-DEVD-FMK) had no effect on the loss of viability. The MPT was measured as the CyA plus ArA- preventable loss of the mitochondrial membrane potential (ΔΨ(m)). The MPT was accompanied by the release of cytochrome c from the mitochondria, caspase-3 activation in the cytosol, cleavage of the nuclear enzyme poly(ADP- ribose)polymerase (PARP), and DNA fragmentation, all of which were inhibited by CyA plus ArA. Z-DEVD-FMK had no effect on the loss of ΔΨ(m) and the redistribution of cytochrome c but did prevent caspase-3 activation, PARP cleavage, and DNA fragmentation. It is concluded that Bax induces the MPT, a critical event in the loss of cell viability. In addition to the cell death, the MPT mediates other typical manifestations of apoptosis in this model, namely release of cytochrome c, caspase activation with PARP cleavage, and DNA fragmentation.

Original languageEnglish
Pages (from-to)7770-7775
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
Publication statusPublished - Mar 27 1998

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ASJC Scopus subject areas

  • Biochemistry

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