Linked Life Data

15215297

Source:http://linkedlifedata.com/resource/pubmed/id/15215297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2004-6-24
pubmed:abstractText
Molecular chaperones and the ubiquitin-proteasome system are participants in the defense against unfolded proteins and provide an effective protein quality control system that is essential for cellular functions and survival. Ubiquitinated tau-positive inclusion bodies containing the small heat shock protein alphaB-crystallin in oligodendrocytes are consistent features of a variety of neurodegenerative diseases, and defects in the proteasome system might contribute to the aggregation process. Oligodendrocytes, the myelin-forming cells of the CNS, are specifically sensitive to stress situations. Here we can show that in cultured rat brain oligodendrocytes proteasomal inhibition by MG-132 or lactacystin caused apoptotic cell death and the induction of heat shock proteins in a time- and concentration-dependent manner. Specifically, alphaB-crystallin was upregulated, and ubiquitinated proteins accumulated. After incubation with MG-132 the tau was dephosphorylated, which enhanced its microtubule-binding capacity. Proteasomal inhibition led to ubiquitination of tau and its association with alphaB-crystallin and to the occurrence of thioflavine S-positive aggregates in the oligodendroglial cytoplasm. These aggregates were positive for tau and also contained ubiquitin and alphaB-crystallin; hence they resembled the glial cytoplasmic inclusions observed in white matter disease and frontotemporal dementias with parkinsonism linked to chromosome 17 (FTDP-17). In summary, the data underscore the specific sensitivity of oligodendrocytes to stress situations and point to a causal relationship of proteasomal impairment and inclusion body formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5748-57
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15215297-Acetylcysteine, pubmed-meshheading:15215297-Animals, pubmed-meshheading:15215297-Apoptosis, pubmed-meshheading:15215297-Brain, pubmed-meshheading:15215297-Cells, Cultured, pubmed-meshheading:15215297-HSP70 Heat-Shock Proteins, pubmed-meshheading:15215297-Heat-Shock Proteins, pubmed-meshheading:15215297-Inclusion Bodies, pubmed-meshheading:15215297-Leupeptins, pubmed-meshheading:15215297-Microtubules, pubmed-meshheading:15215297-Oligodendroglia, pubmed-meshheading:15215297-Oxidative Stress, pubmed-meshheading:15215297-Phosphorylation, pubmed-meshheading:15215297-Proteasome Endopeptidase Complex, pubmed-meshheading:15215297-RNA, Messenger, pubmed-meshheading:15215297-Rats, pubmed-meshheading:15215297-Rats, Wistar, pubmed-meshheading:15215297-Ubiquitin, pubmed-meshheading:15215297-alpha-Crystallin B Chain, pubmed-meshheading:15215297-tau Proteins
pubmed:year
2004
pubmed:articleTitle
Proteolytic stress causes heat shock protein induction, tau ubiquitination, and the recruitment of ubiquitin to tau-positive aggregates in oligodendrocytes in culture.
pubmed:affiliation
Department of Biology, Molecular Neurobiology, University of Oldenburg, D-26111 Oldenburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't