The Bcl-2 oncoprotein functions as a pro-oxidant

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Abstract

The mechanism by which the bcl-2 oncogene exerts its anti-apoptotic and antioxidant action is unknown. We found that expression of bcl-2 in superoxide dismutase-deficient (SOD-) Escherichia coli resulted in increased transcription of the KatG catalase-peroxidase, a 13-fold increase in KatG activity and a 100-fold increase in resistance to hydrogen peroxide. In addition, mutation rate was increased 3-fold, and katG and oxyR, a transcriptional regulator of katG induction, were required for aerobic survival. These data indicate that Bcl-2 acts as a pro-oxidant in E. coli, i.e. Bcl-2 generates reactive oxygen intermediates. In support of a pro- oxidant mechanism in eukaryotic cells, we found a 73% increase in superoxide dismutase activity in a murine B-cell line overexpressing Bcl-2. Increases in reduced glutathione and in oxyradical damage to DNA, previously observed in other overexpressing cell lines, are additional evidence for a pro-oxidant mechanism. Thus, Bcl-2 does not appear to be an antioxidant. Instead, Bcl-2 appears to influence levels of reactive oxygen intermediates that induce endogenous cellular antioxidants. This activity of Bcl-2 may control entry into apoptosis.

Original languageEnglish (US)
Pages (from-to)3487-3490
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number8
StatePublished - 1995

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Oncogene Proteins
Reactive Oxygen Species
Antioxidants
Escherichia coli
Superoxide Dismutase
Cells
Oxygen
Cell Line
Eukaryotic Cells
Mutation Rate
Transcription
Oncogenes
Catalase
Hydrogen Peroxide
Peroxidase
DNA Damage
Glutathione
B-Lymphocytes
Apoptosis
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

The Bcl-2 oncoprotein functions as a pro-oxidant. / Steinman, Howard M.

In: Journal of Biological Chemistry, Vol. 270, No. 8, 1995, p. 3487-3490.

Research output: Contribution to journalArticle

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