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Bcl-2 over-expression promotes genomic instability by inhibiting apoptosis of cells exposed to hydrogen peroxide.
Carcinogenesis 2007; 28(10):2166-71C

Abstract

The anti-apoptotic oncogene bcl-2 is hypothesized to increase the antioxidant status of cells, thereby protecting them from oxidative stress. In this study, we examined hydrogen peroxide (H2O2)-mediated oxidative stress in Jurkat T lymphoma cells. Over-expression of Bcl-2 did not inhibit cytotoxicity at doses of H2O2 that caused necrosis (>200 microM), but it did block cell death at apoptotic doses (<200 microM). However, these cells exhibited the same initial level of protein and lipid oxidation following exposure to H2O2 as the parental cells, indicating that the anti-apoptotic activity is not associated with general antioxidant properties. Bcl-2 expression was able to protect against secondary protein carbonyl formation, which was linked to lysosome stabilization. Assessment of micronuclei formation in cells over-expressing Bcl-2 showed evidence of increased genomic instability, consistent with the impairment of apoptosis in damaged cells. We conclude that while Bcl-2 can block cytotoxicity associated with apoptosis-inducing levels of oxidative stress, it does not protect the cells from the stress itself. Bcl-2 may promote tumourigenesis by preventing the removal of oxidatively damaged cells.

Authors+Show Affiliations

Free Radical Research Group, Department of Pathology, Christchurch School of Medicine & Health Sciences, University of Otago, PO Box 4345, Christchurch, New Zealand.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17434928

Citation

Cox, Andrew G., and Mark B. Hampton. "Bcl-2 Over-expression Promotes Genomic Instability By Inhibiting Apoptosis of Cells Exposed to Hydrogen Peroxide." Carcinogenesis, vol. 28, no. 10, 2007, pp. 2166-71.
Cox AG, Hampton MB. Bcl-2 over-expression promotes genomic instability by inhibiting apoptosis of cells exposed to hydrogen peroxide. Carcinogenesis. 2007;28(10):2166-71.
Cox, A. G., & Hampton, M. B. (2007). Bcl-2 over-expression promotes genomic instability by inhibiting apoptosis of cells exposed to hydrogen peroxide. Carcinogenesis, 28(10), pp. 2166-71.
Cox AG, Hampton MB. Bcl-2 Over-expression Promotes Genomic Instability By Inhibiting Apoptosis of Cells Exposed to Hydrogen Peroxide. Carcinogenesis. 2007;28(10):2166-71. PubMed PMID: 17434928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 over-expression promotes genomic instability by inhibiting apoptosis of cells exposed to hydrogen peroxide. AU - Cox,Andrew G, AU - Hampton,Mark B, Y1 - 2007/04/13/ PY - 2007/4/17/pubmed PY - 2007/12/15/medline PY - 2007/4/17/entrez SP - 2166 EP - 71 JF - Carcinogenesis JO - Carcinogenesis VL - 28 IS - 10 N2 - The anti-apoptotic oncogene bcl-2 is hypothesized to increase the antioxidant status of cells, thereby protecting them from oxidative stress. In this study, we examined hydrogen peroxide (H2O2)-mediated oxidative stress in Jurkat T lymphoma cells. Over-expression of Bcl-2 did not inhibit cytotoxicity at doses of H2O2 that caused necrosis (>200 microM), but it did block cell death at apoptotic doses (<200 microM). However, these cells exhibited the same initial level of protein and lipid oxidation following exposure to H2O2 as the parental cells, indicating that the anti-apoptotic activity is not associated with general antioxidant properties. Bcl-2 expression was able to protect against secondary protein carbonyl formation, which was linked to lysosome stabilization. Assessment of micronuclei formation in cells over-expressing Bcl-2 showed evidence of increased genomic instability, consistent with the impairment of apoptosis in damaged cells. We conclude that while Bcl-2 can block cytotoxicity associated with apoptosis-inducing levels of oxidative stress, it does not protect the cells from the stress itself. Bcl-2 may promote tumourigenesis by preventing the removal of oxidatively damaged cells. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/17434928/Bcl_2_over_expression_promotes_genomic_instability_by_inhibiting_apoptosis_of_cells_exposed_to_hydrogen_peroxide_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgm093 DB - PRIME DP - Unbound Medicine ER -