Multiple protective functions of catalase against intercellular apoptosis-inducing ROS signaling of human tumor cells
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Sonja Heinzelmann
Abstract
Tumor cells are protected against intercellular reactive oxygen species (ROS)-mediated apoptosis signaling mediated by the HOCl and/or the nitric oxide (NO)/peroxynitrite signaling pathway. We have recently shown that tumor cell resistance against HOCl signaling can be abrogated through inhibition of catalase. The protection of tumor cells against the NO/peroxynitrite signaling pathway has remained enigmatic so far. Here, we show that suboptimal inhibition of catalase by 3-aminotriazole or a monoclonal antibody against catalase, as well as partial knockdown of catalase by specific siRNA allows selective reactivation of the NO/peroxynitrite pathway in MKN 45 gastric carcinoma cells, followed by the HOCl pathway at higher inhibitor or siRNA concentrations. In SKN-MC Ewing sarcoma cells, catalase inhibition causes apoptosis induction solely based on the NO/peroxynitrite pathway. Protection against NO/peroxynitrite signaling is shown to be due to the potential of catalase to decompose peroxynitrite. The direct interaction of catalase with peroxynitrite is verified through the detection of compound I (CAT FeIV=O+·) after the interaction of peroxynitrite with catalase. In a complementary experiment, addition of catalase protects sensitive transformed cells against ROS-mediated apoptosis induction. Thus, the expression of membrane-associated catalase is sufficient to protect tumor cells against multiple intercellular ROS-mediated signaling pathways.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Guest Editorial
- Highlight: Molecular Neurobiology
- HIGHLIGHT: MOLECULAR NEUROBIOLOGY
- Actin-mediated gene expression in neurons: the MRTF-SRF connection
- RIM proteins and their role in synapse function
- Brain tumor stem cells
- The mitochondria permeability transition pore complex in the brain with interacting proteins – promising targets for protection in neurodegenerative diseases
- Involvement of the calcium sensor GCAP1 in hereditary cone dystrophies
- Live cell imaging of cytoskeletal dynamics in neurons using fluorescence photoactivation
- REVIEWS
- Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions
- Cathepsin L in metastatic bone disease: therapeutic implications
- GENES AND NUCLEIC ACIDS
- Activity-based selection of HIV-1 reverse transcriptase variants with decreased polymerization fidelity
- CELL BIOLOGY AND SIGNALING
- Multiple protective functions of catalase against intercellular apoptosis-inducing ROS signaling of human tumor cells
- Molecular characterisation of ‘transmembrane protein 192’ (TMEM192), a novel protein of the lysosomal membrane
- PROTEOLYSIS
- Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases
