RGD Reference Report - Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy. - Rat Genome Database

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Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy.

Authors: Pountney, DL  Dickson, TC  Power, JH  Vickers, JC  West, AJ  Gai, WP 
Citation: Pountney DL, etal., Neurotox Res. 2011 Jan;19(1):115-22. Epub 2009 Dec 29.
RGD ID: 6480516
Pubmed: PMID:20039155   (View Abstract at PubMed)
DOI: DOI:10.1007/s12640-009-9146-6   (Journal Full-text)

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterised by Parkinsonian and autonomic symptoms and by widespread intracytoplasmic inclusion bodies in oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are comprised of 9-10 nm filaments rich in the protein alpha-synuclein, also found in neuronal inclusion bodies associated with Parkinson's disease. Metallothioneins (MTs) are a class of low-molecular weight (6-7 kDa), cysteine-rich metal-binding proteins the expression of which is induced by heavy metals, glucocorticoids, cytokines and oxidative stress. Recent studies have shown a role for the ubiquitously expressed MT-I/II isoforms in the brain following a variety of stresses, whereas, the function of the brain-specific MT isoform, MT-III, is less clear. MT-III and MT-I/II immunostaining of post-mortem tissue in MSA and normal control human brains showed that the number of MT-III-positive cells is significantly increased in MSA in visual cortex, whereas MT-I/II isoforms showed no significant difference in the distribution of immunopositive cells in MSA compared to normal tissue. GCIs were immunopositive for MT-III, but were immunonegative for the MT-I/II isoforms. Immunofluorescence double labelling showed the co-localisation of alpha-synuclein and MT-III in GCIs in MSA tissue. In isolated GCIs, transmission electron microscopy demonstrated MT-III immunogold labelling of the amorphous material surrounding alpha-synuclein filaments in GCIs. High-molecular weight MT-III species in addition to MT-III monomer were detected in GCIs by Western analysis of the detergent-solubilised proteins of purified GCIs. These results show that MT-III, but not MT-I/II, is a specific component of GCIs, present in abnormal aggregated forms external to the alpha-synuclein filaments.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MT3Humanmultiple system atrophy  IEP protein: increased expression: visual cortexRGD 
Mt3Ratmultiple system atrophy  ISOMT3 (Homo sapiens)protein: increased expression: visual cortexRGD 
Mt3Mousemultiple system atrophy  ISOMT3 (Homo sapiens)protein: increased expression: visual cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mt3  (metallothionein 3)

Genes (Mus musculus)
Mt3  (metallothionein 3)

Genes (Homo sapiens)
MT3  (metallothionein 3)


Additional Information