Reactive oxygen species are downstream mediators of p53-dependent apoptosis

Thomas M. Johnson, Zu Xi Yu, Victor J. Ferrans, Robert A. Lowenstein, Toren Finkel

Research output: Contribution to journalArticle

Abstract

Reactive oxygen species (ROS) have been implicated as potential modulators of apoptosis. Conversely, experiments under hypoxic conditions have suggested that apoptosis could occur in the absence of ROS. We sought to determine whether a central modulator of apoptosis, p53, regulates the levels of intracellular ROS and whether a rise in ROS levels is required for the induction of p53-dependent apoptosis. We transiently overexpressed wild-type p53, using adenoviral gene transfer, and identified cell types that were sensitive or resistant to p53-mediated apoptosis. Cells sensitive to p53- mediated apoptosis produced ROS concomitantly with p53 overexpression, whereas cells resistant to p53 failed to produce ROS. In sensitive cells, both ROS production and apoptosis were inhibited by antioxidant treatment. These results suggest that p53 acts to regulate the intracellular redox state and induces apoptosis by a pathway that is dependent on ROS production.

Original languageEnglish (US)
Pages (from-to)11848-11852
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996
Externally publishedYes

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Reactive Oxygen Species
Apoptosis
Oxidation-Reduction
Antioxidants
Genes

Keywords

  • adenovirus
  • antioxidants
  • atherosclerosis
  • restenosis
  • smooth muscle cell

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Reactive oxygen species are downstream mediators of p53-dependent apoptosis. / Johnson, Thomas M.; Yu, Zu Xi; Ferrans, Victor J.; Lowenstein, Robert A.; Finkel, Toren.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 21, 15.10.1996, p. 11848-11852.

Research output: Contribution to journalArticle

Johnson, Thomas M. ; Yu, Zu Xi ; Ferrans, Victor J. ; Lowenstein, Robert A. ; Finkel, Toren. / Reactive oxygen species are downstream mediators of p53-dependent apoptosis. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 21. pp. 11848-11852.
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