TY - JOUR
T1 - The Bcl-2 oncoprotein functions as a pro-oxidant
AU - Steinman, H. M.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7876080
AN - SCOPUS:0028910217
SN - 0021-9258
VL - 270
SP - 3487
EP - 3490
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -