Hydroxylamine potentiates the effect of low dose hydrogen peroxide in glioma cells independent of p53 |
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Authors: | Datta Kamal Mathur Srinivas G Srivastava Tapasya Shah Preeti Chattopadhyay Parthaprasad Sinha Subrata |
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Affiliation: | Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India |
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Abstract: | We had earlier shown that higher concentration of hydrogen peroxide (H2O2) induced p53-dependent apoptosis in glioma cell line with wild type p53 but had minimal effect on cells with mutated p53. Here we show a potentiating effect of hydroxylamine (HA), an inhibitor of catalase, on a nontoxic dose of H2O2 in glioma cells. HA sensitized both p53 wild type and mutated glioma cells to 0.25 mM H2O2. Potentiating effect of HA was independent of p53. Higher levels of reactive oxygen species (ROS) generation were observed in cells treated with HA+H2O2 as compared to cells treated with each component alone in both the cell lines. Dimethyl sulfoxide (DMSO) protected cells. Cytosolic cytochrome c and activated caspase 3 were detected at 4 h. The results suggest that higher levels of intracellular ROS, generated by HA+H2O2 act as a molecular switch in activating a rapidly acting p53-independent mitochondrial apoptotic pathway. |
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Keywords: | Reactive oxygen species Cell death Antisense Cytochrome c Mitochondrial pathway |
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