Cell Biology International · 2011 · 18 citations · 20 references
Life SciencesCancer BiologyChemotherapyMechanisms Of ToxicityMolecular OncologyBcl-2 Family ProteinsMolecular Mechanisms Of ToxicityOxidative StressOxidative Stress MechanismsTelomere BiologyTelomere MaintenanceBcl-2 Protein ExpressionOxidative Stress ToxicityReactive Oxygen Species GenerationTelomerase ActivationTelomerase Activity AssessmentTelomerase EnzymeTelomerase FunctionTelomerase Regulation
We have analysed telomerase activity to determine whether it can be modified when BCL-2 is endogenously overexpressed in response to a mild oxidative stress treatment as part of a survival mechanism, in contrast with an exogenous bcl-2 overexpression due to a retroviral infection. Endogenous bcl-2 overexpression was induced after a low oxidative insult of H2O2 in mice primary lung fibroblasts and L929 cell, whereas bcl-2 exogenous overexpression was performed using a retroviral infection in L929 cells. Telomerase activity was quantified in Bcl-2 overexpressing cells by the TRAP assay. When the cells were treated with different H2O2 concentrations, only those exposed to 50 μM showed increased telomerase activity. This correlates with BCL-2 expression as part of the endogenous response to mild oxidative stress. Oxidative stress generated during the toxic mechanism of chemotherapeutic drugs might induce BCL-2 increment, enhancing telomerase activity and reactivating the oncogenic process. Clinical trials should take into consideration the possibility of telomerase activation following increased BCL-2 expression when treating patients with ROS (reactive oxygen species) generation by anti-cancer drugs.
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