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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18279

Title: The Effects of Oxidative Stress on Calcineurin Activity and DJ-1 Subcellular Localization
Authors: Diec, Diana
Advisor: Mills, Linda
Department: Physiology
Keywords: oxidative stress
DJ-1, calcineurin
Issue Date: 14-Jan-2010
Abstract: Oxidative stress and mutations in DJ-1, a redox sensitive protein, are linked to Parkinson's Disease. The protective mechanism of DJ-1 is unclear. I hypothesized that: 1) DJ-1 mediates protection by translocating to mitochondria after oxidative stress and, 2) when DJ-1 is downregulated, apoptotic pathways regulated by calcineurin are also downregulated. In PC12 cells and rat cortical neurons, oxidative stress resulted in the upregulation of DJ-1 and increased DJ-1 in the nucleus, but did not increase mitochondrial translocation of DJ-1. In cortical neurons and wildtype mouse embryonic fibroblasts, H2O2 induced cleavage of CnA into an inactive fragment. DJ-1 knockout fibroblasts had less nuclear localization of the transcription factor NFATc4, a substrate of calcineurin involved in apoptosis. H2O2 increased CnA cleavage in DJ-1 knockout fibroblasts, but NFATc4 localization was unchanged. These results suggest that the downregulation of apoptotic pathways regulated by calcineurin may be a compensatory response to the downregulation of DJ-1.
URI: http://hdl.handle.net/1807/18279
Appears in Collections:Master
Department of Physiology - Master theses

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