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.

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.