Hydroxylamine potentiates the effect of low dose hydrogen peroxide in glioma cells independent of p53.
We had earlier shown that higher concentration of hydrogen peroxide (H(2)O(2)) 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 H(2)O(2) in glioma cells. HA sensitized both p53 wild type and mutated glioma cells to 0.25 mM H(2)O(2). Potentiating effect of HA was independent of p53. Higher levels of reactive oxygen species (ROS) generation were observed in cells treated with HA+H(2)O(2) 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 4h. The results suggest that higher levels of intracellular ROS, generated by HA+H(2)O(2) act as a molecular switch in activating a rapidly acting p53-independent mitochondrial apoptotic pathway.
Datta
Kamal
K
Department of Biochemistry, All India Institute of Medical Sciences, 110029 New Delhi, India.
Mathur
Srinivas G
SG
Srivastava
Tapasya
T
Shah
Preeti
P
Chattopadhyay
Parthaprasad
P
Sinha
Subrata
S
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D004789:Enzyme Activation; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019811:Hydroxylamine / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016877:Oxidants; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D019811:Hydroxylamine; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004121:Dimethyl Sulfoxide