The course of etoposide-induced apoptosis in jurkat cells lacking p53 and Bax

Natalie O. Karpinich, Marco Tafani, Timothy Schneider, Matteo A. Russo, John L. Farber

Research output: Contribution to journalArticle

Abstract

Jurkat T-lymphocytes lack p53 and Bax but contain p73 and Bid and are killed by etoposide (ETO). With ETO c-abl is phosphorylated and phosphorylated p73 increased. Translocation of full-length Bid to mitochondria follows, with induction of the mitochondrial permeability transition (MPT) and release of cytochrome c into the cytosol. Pronounced swelling of mitochondria was evident ultrastructurally, and the MPT inhibitor cyclosporin A prevented the release of cytochrome c. Overexpression of Bcl-2 prevented the translocation of Bid, the release of cytochrome c, and cell death. The pan-caspase inhibitor ZVAD-FMK prevented the cell killing, but not the initial release of cytochrome c. An accumulation of tBid occurred at later times in association with Bid degradation. A sequence is proposed that couples DNA damage to Bid translocation via activation of c-abl and p73. Bid translocation induces the MPT, the event that causes release of cytochrome c, activation of caspases, and cell death.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalJournal of Cellular Physiology
Volume208
Issue number1
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Jurkat Cells
Etoposide
Cytochromes c
Apoptosis
Permeability
Mitochondria
Cell death
Cell Death
Chemical activation
Caspase Inhibitors
T-cells
Caspases
Cytosol
Cyclosporine
DNA Damage
Swelling
Cells
Association reactions
T-Lymphocytes
Degradation

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

The course of etoposide-induced apoptosis in jurkat cells lacking p53 and Bax. / Karpinich, Natalie O.; Tafani, Marco; Schneider, Timothy; Russo, Matteo A.; Farber, John L.

In: Journal of Cellular Physiology, Vol. 208, No. 1, 07.2006, p. 55-63.

Research output: Contribution to journalArticle

Karpinich, Natalie O. ; Tafani, Marco ; Schneider, Timothy ; Russo, Matteo A. ; Farber, John L. / The course of etoposide-induced apoptosis in jurkat cells lacking p53 and Bax. In: Journal of Cellular Physiology. 2006 ; Vol. 208, No. 1. pp. 55-63.
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