Linked Life Data

12528814

Source:http://linkedlifedata.com/resource/pubmed/id/12528814

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-16
pubmed:abstractText
Cortical and striatal perinuclear cytoplasmic aggregates and intranuclear inclusions of mutant huntingtin are neuropathological hallmarks of Huntington disease (HD). Although the mechanisms involved in the formation of these aggregates are unclear, a recent hypothesis implicates cross-linking of mutant huntingtin protein into aggregates by transglutaminase. This study explores the hypothesis that transglutaminase catalyzes cross-linking of huntingtin into intranuclear inclusions. Using immunofluorescence and confocal microscopy we demonstrate 99% colocalization of transglutaminase-catalyzed epsilon-(gamma-glutamyl) lysine covalent cross-links with nuclear aggregates of huntingtin protein in the frontal cortex of postmortem HD brain tissue. Furthermore, the transglutaminase 2 isoform colocalizes with both huntingtin protein and epsilon-(gamma-glutamyl) lysine covalent cross-links in HD intranuclear inclusions. Transient transfection of N-terminally truncated huntingtin with an expanded glutamine domain (htt-N63-148Q-myc) with and without and transglutaminase 2 into HEK 293T cells resulted in an increase in cross-linked huntingtin in the insoluble formic acid-treated pellet in comparison to transfection of N-terminally truncated huntingtin with normal length glutamine domain (htt-N63-18Q-myc). Transfection with both htt-N63-148Q-myc and transglutaminase 2 resulted in high molecular weight huntingtin in the insoluble fraction. These data support the hypothesis that transglutaminase catalyzed cross-linking of mutant huntingtin is involved in the formation and/or stabilization of huntingtin protein aggregates in HD. Based on these and other studies, modulation of transglutaminase activity could be explored as a treatment for HD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Transglutaminase cross-links in intranuclear inclusions in Huntington disease.
pubmed:affiliation
Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois 60153, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.