Skip to main content
Article thumbnail
Location of Repository

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

By Stéphanie Baulac, Hope Lu, Jennifer Strahle, Ting Yang, Matthew S Goldberg, Jie Shen, Michael G Schlossmacher, Cynthia A Lemere, Qun Lu and Weiming Xia


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

Topics: Research Article
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2007). Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Mol Neurodegener
    2. (2004). al.: DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia. Ann Neurol
    3. (2006). Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease.
    4. (2007). Bandopadhyay R: DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders. Neurobiol Dis
    5. (1991). Braak E: Neuropathological stageing of Alzheimerrelated changes.
    6. (2001). CB: Inhibition of zebrafish fgf8 pre-mRNA splicing with morpholino oligos: a quantifiable method for gene knockdown. Genesis
    7. (2000). CB: islet reveals segmentation in the Amphioxus hindbrain homolog. Dev Biol
    8. (2002). Cheng KC: A call to fins! Zebrafish as a gerontological model. Aging Cell
    9. (2002). Corrocher R: A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism. Clin Exp Med
    10. (2004). Dimerization of Parkinson disease-causing DJ-1 and formation of high molecular weight complexes containing parkin in human brain. Mol Cell Neurosci
    11. (2006). EA: Zebrafish DJ-1 is evolutionarily conserved and expressed in dopaminergic neurons. Brain Res
    12. (1998). Early neuromeric distribution of tyrosinehydroxylase-immunoreactive neurons in human embryos.
    13. (2000). Ekker SC: Effective targeted gene 'knockdown' in zebrafish.
    14. (2008). Eliezer D: Structural effects of Parkinson's disease linked DJ-1 mutations. Protein Sci
    15. (2008). Enhanced oxidative stress is an early event during development of Alzheimer-like pathologies in presenilin conditional knock-out mice. Neurosci Lett
    16. (2004). et al.: Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron
    17. (2008). et al.: DJ-1-binding compounds prevent oxidative stress-induced cell death and movement defect in Parkinson's disease model rats.
    18. (2007). et al.: DJ1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc Natl Acad Sci USA
    19. (2004). et al.: Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron
    20. et al.: Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.
    21. (2008). G: DJ-1 decreases Bax expression through repressing p53 transcriptional activity.
    22. (1996). Goping G: The MPTP-induced parkinsonian syndrome in the goldfish is associated with major cell destruction in the forebrain and subtle changes in the optic tectum. Exp Neurol
    23. (2004). Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science
    24. (2008). HS: DJ-1 modulates UVinduced oxidative stress signaling through the suppression of MEKK1 and cell death. Cell Death Differ
    25. (2005). Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci USA
    26. (2008). Ito Y: Comparative study of hydrogen peroxide- and 4-hydroxy2-nonenal-induced cell death in HT22 cells. Neurochem Int
    27. (2004). Kaelin-Lang A: Localization of DJ-1 mRNA in the mouse brain. Neurosci Lett
    28. (1995). Kuijpers GA: Effect of MPTP on dopaminergic neurons in the goldfish brain: a light and electron microscope study. Brain Res
    29. (1990). L: Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in goldfish brain. Brain Res
    30. (2006). L: Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases.
    31. (2001). Larson JD: Morphant technology in model developmental systems. Genesis
    32. (2000). Lemere CA: Temporal accrual of complement proteins in amyloid plaques in Down's syndrome with Alzheimer's disease.
    33. (2004). LS: Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein folding and function.
    34. (2008). MF: Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med
    35. (1997). Mutation In the Alpha-Synuclein Gene Identified In Families With Parkinsons Disease. Science
    36. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature
    37. (2005). Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron
    38. (2007). O: p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease.
    39. (1994). Okamoto H: Developmental regulation of islet-1 mRNA expression during neuronal differentiation in embryonic zebrafish. Dev Dyn
    40. (2003). oxidative damage, and inflammation in Parkinson's disease.
    41. (2008). Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology
    42. (2007). Paricio N: Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene
    43. (2004). Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease. Acta Neuropathol (Berl)
    44. (1992). RG: An immunohistochemical study of the telencephalon of the senegal bichir (Polypterus senegalus).
    45. (1995). Schilling TF: Stages of embryonic development of the zebrafish. Dev Dyn
    46. (2009). Selkoe DJ: A Specific ELISA for Measuring Amyloid β-Protein Oligomer in Human Plasma and the Brains of Alzheimer Patients. Arch Neurol
    47. (2004). Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease. Neurotoxicol Teratol
    48. (1993). Structure of the zebrafish snail1 gene and its expression in wild-type, spadetail, and no tail mutant embryos. Development
    49. (2008). Sumoylation is critical for DJ-1 to repress p53 transcriptional activity. FEBS Lett
    50. (1992). T: Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. Science
    51. (2003). The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. Brain 2004, 127(Pt 2):420-430. Epub
    52. (1994). The Zebrafish Book Eugene, OR:
    53. (1997). Thomas JB: The Drosophila islet gene governs axon pathfinding and neurotransmitter identity. Neuron
    54. (2006). Ting JP: DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci USA
    55. (1993). Umeda M: A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature
    56. (2006). Xia W: Zebrafish lacking Alzheimer Presenilin Enhancer 2 (Pen-2) demonstrate excessive p53 dependent apoptosis and neuronal loss.
    57. (1992). Youdim MB: A parkinsonian syndrome induced in the goldfish by the neurotoxin MPTP. Faseb J
    58. (1993). Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation. Development
    59. (2008). Zhang B: Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Dev Biol

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.