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The expression of DJ‐1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease

Bandopadhyay, Rina ; Kingsbury, Ann E. ; Cookson, Mark R. ; Reid, Andrew R. ; Evans, Ian M. ; Hope, Andrew D. ; Pittman, Alan M. ; Lashley, Tammaryn ; Canet‐Aviles, Rosa ; Miller, David W. ; McLendon, Chris ; Strand, Catherine ; Leonard, Andrew J. ; Abou‐Sleiman, Patrick M. ; Healy, Daniel G. ; Ariga, Hiroyashi ; Wood, Nicholas W. ; de Silva, Rohan ; Revesz, Tamas ; Hardy, John A. ; Lees, Andrew J.

Brain (London, England : 1878), 2004-02, Vol.127 (2), p.420-430 [Periódico revisado por pares]

Oxford: Oxford University Press

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Título:
The expression of DJ‐1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease
Autor: Bandopadhyay, Rina ; Kingsbury, Ann E. ; Cookson, Mark R. ; Reid, Andrew R. ; Evans, Ian M. ; Hope, Andrew D. ; Pittman, Alan M. ; Lashley, Tammaryn ; Canet‐Aviles, Rosa ; Miller, David W. ; McLendon, Chris ; Strand, Catherine ; Leonard, Andrew J. ; Abou‐Sleiman, Patrick M. ; Healy, Daniel G. ; Ariga, Hiroyashi ; Wood, Nicholas W. ; de Silva, Rohan ; Revesz, Tamas ; Hardy, John A. ; Lees, Andrew J.
Assuntos: 2D gel electrophoresis ; 2DGE = two‐dimensional gel electrophoresis ; Aged ; Aged, 80 and over ; Animals ; Antibodies, Monoclonal - immunology ; Astrocytes - metabolism ; Biological and medical sciences ; Blotting, Western ; Brain ; Brain - metabolism ; Cells, Cultured ; DA = dopaminergic ; Diseases ; DJ‐1 ; Female ; Frontal Lobe - metabolism ; Genetics ; GFAP = glial fibrillary acidic protein ; Hippocampus - metabolism ; Humans ; immunohistochemistry ; immunoreactive ; Intracellular Signaling Peptides and Proteins ; IR = immunoreactivity ; LB = Lewy body ; Lewy Bodies - metabolism ; Lewy Bodies - ultrastructure ; LN =Lewy neurite ; Male ; Medical sciences ; Mice ; Neurological Impairments ; Neurology ; Neurons - metabolism ; Oncogene Proteins - immunology ; Oncogene Proteins - metabolism ; Oxidative Stress ; paraquat ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson’s disease ; Protein Deglycase DJ-1 ; Protein Isoforms - metabolism ; PSP = progressive supranuclear palsy ; SN = substantia nigra ; Substantia Nigra - metabolism
É parte de: Brain (London, England : 1878), 2004-02, Vol.127 (2), p.420-430
Notas: istex:DA4BE02115489AC02CA2DEC2C405944536F3A03F
Correspondence to: Professor Andrew J. Lees MD, FRCP, Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, 46 Cleveland Street, London W1T 4JF, UK. E‐mail: a.lees@ion.ucl.ac.uk
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Descrição: Two mutations in the DJ‐1 gene on chromosome1p36 have been identified recently to cause early‐onset, autosomal recessive Parkinson’s disease. As no information is available regarding the distribution of DJ‐1 protein in the human brain, in this study we used a monoclonal antibody for DJ‐1 to map its distribution in frontal cortex and substantia nigra, regions invariably involved in Parkinson’s disease. Western blotting of human frontal cortex showed DJ‐1 to be an abundant protein in control, idiopathic Parkinson’s disease, cases with clinical and pathological phenotypes of Parkinson’s disease with R98Q polymorphism for DJ‐1, and in progressive supranuclear palsy (PSP) brains. We also showed that DJ‐1 immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic processes in both control and Parkinson’s disease frontal cortex, whereas neurons showed light or no DJ‐1 IR. Only occasional Lewy bodies (LBs), the pathological hallmarks of Parkinson’s disease, showed faint DJ‐1 IR, localized to the outer halo. In preclinical studies we showed that DJ‐1 is expressed in primary hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also showed multiple pI isoforms for DJ‐1 ranging between 5.5–6.6 in both control and Parkinson’s disease brains, whilst exposure of M17 cells to the oxidizing agent paraquat was manifested as a shift in pI of endogenous DJ‐1 towards more acidic isoforms. We conclude that DJ‐1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions. These results are consistent with the hypothesis that neuronal–glial interactions are important in the pathophysiology of Parkinson’s disease.
Editor: Oxford: Oxford University Press
Idioma: Inglês

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The expression of DJ‐1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease

Oxford: Oxford University Press

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