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

516 Citations (Scopus)

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

Fingerprint

Cell death
Poly(ADP-ribose) Polymerases
Permeability
Cell Death
Cytochromes c
Caspase 3
Cyclosporine
DNA Fragmentation
Chemical activation
DNA
Mitochondria
T-cells
Caspases
Aspartic Acid
Caspase Inhibitors
Jurkat Cells
Mitochondrial Membrane Potential
Cytosol
Cells
Apoptosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. / Pastorino, John G.; Chen, Sing Tsung; Tafani, Marco; Snyder, Jack W.; Farber, John L.

In: Journal of Biological Chemistry, Vol. 273, No. 13, 27.03.1998, p. 7770-7775.

Research output: Contribution to journalArticle

Pastorino, John G. ; Chen, Sing Tsung ; Tafani, Marco ; Snyder, Jack W. ; Farber, John L. / The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 13. pp. 7770-7775.
@article{bf7f6a9a40db41bdbc4e8c2b6630d78c,
title = "The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition",
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.",
author = "Pastorino, {John G.} and Chen, {Sing Tsung} and Marco Tafani and Snyder, {Jack W.} and Farber, {John L.}",
year = "1998",
month = "3",
day = "27",
doi = "10.1074/jbc.273.13.7770",
language = "English",
volume = "273",
pages = "7770--7775",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "13",

}

TY - JOUR

T1 - The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition

AU - Pastorino, John G.

AU - Chen, Sing Tsung

AU - Tafani, Marco

AU - Snyder, Jack W.

AU - Farber, John L.

PY - 1998/3/27

Y1 - 1998/3/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032571294&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032571294&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.13.7770

DO - 10.1074/jbc.273.13.7770

M3 - Article

C2 - 9516487

AN - SCOPUS:0032571294

VL - 273

SP - 7770

EP - 7775

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 13

ER -