Linked Life Data

16775387

Source:http://linkedlifedata.com/resource/pubmed/id/16775387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-6-15
pubmed:abstractText
Aceruloplasminemia is a neurodegenerative disease characterized by parenchymal iron accumulation owing to mutations in the ceruloplasmin gene. Ceruloplasmin is expressed in the central nervous system in which most of the ceruloplasmin is located on the surface of astrocytes in a glycosylphosphatidylinositol (GPI)-anchored form. We herein describe the biochemical features of wild-type and mutant GPI-anchored ceruloplasmin. An overexpression of wild-type GPI-anchored ceruloplasmin in Chinese hamster ovary cells led to the formation of aggresome-like inclusions, especially in the presence of proteasome inhibitors. As expected from the properties of aggresomes, the inclusions were colocalized with gamma-tubulin and a disruption of microtubules using nocodazole blocked the formation of such inclusions. Aceruloplasminemia-linked mutant proteins failed to form such inclusions even after treatment with proteasomal inhibitors. An immunofluorescent analysis indicated that the mutant proteins were thus retained in the endoplasmic reticulum (ER), whereas the transfected cells showed a decreased viability. The expression of glucose-regulated protein 78 that is one of the ER stress sensor proteins, and the activity of glucose-regulated protein 78 promoter was upregulated in the cells transfected with the mutants. These findings indicated that when the overexpressed cytoplasmic wild-type ceruloplasmin was not subjected to degradation by the proteasome-ubiquitin system, then the wild-type protein was transported along the microtubules, thus forming inclusions at the microtubule organizing center, whereas the mutant ceruloplasmin failed to form any such inclusions, because the mutant protein might not have been translocated across the ER into the cytoplasm. Therefore, the mutant protein was considered to have accumulated in the ER thus leading to the ER stress, which resulted in cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1535-1084
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
361-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia.
pubmed:affiliation
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't