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Scavenging of extracellular H2O2 by catalase inhibits the proliferation of HER-2/Neu-transformed rat-1 fibroblasts through the induction of a stress response

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dc.contributor.author Preston, T. J. en_US
dc.contributor.author Muller, W. J. en_US
dc.contributor.author Singh, G. en_US
dc.date.accessioned 2006-06-22T14:16:51Z
dc.date.available 2006-06-22T14:16:51Z
dc.date.issued 2001-03 en_US
dc.identifier.citation J Biol Chem 276, 9558-64 (2001) en_US
dc.identifier.uri http://hdl.handle.net/1807.1/186
dc.description This article is hosted on a website external to the CBCRA Open Access Archive. Selecting “View/Open” below will launch the full-text article in another browser window.
dc.description.abstract High levels of reactive oxygen species (ROS) are associated with cytotoxicity. Alternatively, nontoxic levels of ROS like hydrogen peroxide (H(2)O(2)) can mediate the transmission of many intracellular signals, including those involved in growth and transformation. To identify pathways downstream of endogenous cellular H(2)O(2) production, the response of Rat-1 fibroblasts exhibiting differential HER-2/Neu receptor tyrosine kinase activity to removal of physiological H(2)O(2) concentrations was investigated. The proliferation of all cells was abolished by addition of the H(2)O(2) scavenger catalase to the culture medium. HER-2/Neu activity was not significantly affected by catalase treatment, suggesting that the target(s) of the H(2)O(2) signal lie downstream of the receptor in our model. ERK1/2 phosphorylation was blocked by catalase in fibroblasts expressing wild type Neu, however such a response did not occur in cells possessing activated mutant Neu. This indicates that the ERK1/2 response contributes little to the growth inhibition observed. By contrast, JNK1 activity increased following the addition of catalase or H(2)O(2), regardless of Neu activity or level of cell transformation. Phosphorylation of p38 MAPK was induced by H(2)O(2) but not by catalase. These observations suggest that scavenging of H(2)O(2) from the cellular environment blocks Rat-1 proliferation primarily through the activation of stress pathways. en_US
dc.description.provenance Made available in DSpace on 2006-06-22T14:16:51Z (GMT). No. of bitstreams: 1 Preston.2001.9558.html: 413 bytes, checksum: f25a0edfd03a29e5cb03a64963ab0bcd (MD5) Previous issue date: 2001-03 en
dc.format.extent 413 bytes
dc.format.mimetype text/html
dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology en_US
dc.relation.uri http://www.asbmb.org/ en_US
dc.title Scavenging of extracellular H2O2 by catalase inhibits the proliferation of HER-2/Neu-transformed rat-1 fibroblasts through the induction of a stress response en_US
dc.type Article en_US

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