2,5-Hexanedione-induced intermediate filament aggregates contain ubiquitin-protein conjugate immunoreactivity and resemble Rosenthal fibres.
A number of chronic degenerative disorders including cerebellar astrocytomas and Parkinson's disease are characterized by the presence of cytosolic inclusions which contain intermediate filament (IF) aggregates and ubiquitin-protein conjugate immunoreactivity. In cerebellar astrocytomas these inclusions are known as Rosenthal fibres. 2,5-hexanedione (HD) treatment is known to induce IF aggregates in cells in culture. HD-induced aggregates have therefore been studied as a potential model for the clinical inclusions. Exposure of astrocyte cultures to 2 mM HD for 2 or 4 weeks led to the formation of aggregates of the IFs (glial fibrillary acidic protein and vimentin). The aggregates contained ubiquitin-protein conjugates, which, on electron microscopy appeared to be localized in a peripheral shell. In addition, ubiquitin mRNA levels were found to be elevated approximately threefold by HD treatment. HD-induced inclusions and Rosenthal fibres were found to share a number of features. HD administration, therefore, appears to be a suitable model for the production of pathological inclusions.
Tuckwell
D S
DS
Department of Biochemistry and Molecular Biology, University of Manchester.
László
L
L
Mayer
R J
RJ
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001254:Astrocytoma / Q000648:ultrastructure*; D015152:Blotting, Northern; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000648:ultrastructure*; D006588:Hexanones / Q000494:pharmacology*; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014452:Ubiquitins / Q000378:metabolism*
D006588:Hexanones; D007381:Intermediate Filament Proteins; D014452:Ubiquitins; C011269:2,5-hexanedione