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Increased DJ-1 expression under oxidative stress and in Alzheimer's disease brains

Stéphanie Baulac1 email, Hope Lu1 email, Jennifer Strahle1 email, Ting Yang1 email, Matthew S Goldberg1,4 email, Jie Shen1 email, Michael G Schlossmacher1 email, Cynthia A Lemere1 email, Qun Lu2,3 email and Weiming Xia1 email

Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA

Harriet and John Wooten Laboratory of Alzheimer's Disease Research, The Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

Department of Anatomy and Cell Biology, The Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

Departments of Neurology and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8813, USA

author email corresponding author email

Molecular Neurodegeneration 2009, 4:12doi:10.1186/1750-1326-4-12

Published: 25 February 2009

Abstract

Mutations in the DJ-1 gene have been linked to autosomal recessive familial Parkinson's disease. To understand the function of DJ-1, we determined the DJ-1 expression in both zebrafish and post mortem human brains. We found that DJ-1 was expressed early during zebrafish development and throughout adulthood. Knock down (KD) of DJ-1 by injection of morpholino did not cause dramatic morphologic alterations during development, and no loss of dopaminergic neurons was observed in embryos lacking DJ-1. However, DJ-1 KD embryos were more susceptible to programmed cell death. While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos. Interestingly, DJ-1 expression was increased in brains of zebrafish under conditions of oxidative stress, indicating that DJ-1 is a part of stress-responsive machinery. Since oxidative stress is one of the major contributors to the development of Alzheimer's disease (AD), we also examined DJ-1 expression in AD brains. Using DJ-1 specific antibodies, we failed to detect a robust staining of DJ-1 in brain tissues from control subjects. However, DJ-1 immunoreactivity was detected in hippocampal pyramidal neurons and astrocytes of AD brains. Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains.


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