Linked Life Data

14654368

Source:http://linkedlifedata.com/resource/pubmed/id/14654368

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-12-5
pubmed:abstractText
A missense mutation R141W in the strong tropomyosin-binding region of cardiac troponin T (cTnT) has recently been reported to cause dilated cardiomyopathy (DCM), following the first report of a DCM-causing deletion mutation DeltaK210. To clarify the molecular mechanism for the pathogenesis of DCM caused by this novel mutation in cTnT gene, functional analyses were made on the recombinant human cTnT mutant proteins. Exchanging human wild-type and mutant cTnTs into rabbit skinned cardiac muscle fibers revealed that R141W mutation resulted in a decrease in the Ca(2+) sensitivity of force generation, as in the case of DeltaK210 mutation lying outside the strong tropomyosin-binding region. In contrast, a missense mutation R94L in the vicinity of the strong tropomyosin-binding region associated with hypertrophic cardiomyopathy (HCM) resulted in an increase in the Ca(2+) sensitivity of force generation, as in the case of the other HCM-causing mutations in cTnT reported previously. An assay using a quartz-crystal microbalance (a very sensitive mass-measuring device) revealed that R141W mutation increased the affinity of cTnT for alpha-tropomyosin by approximately three times, whereas an HCM-causing mutation DeltaE160 in the strong tropomyosin-binding region, as well as DeltaK210 and R94L mutations, had no effects on the interaction between cTnT and alpha-tropomyosin. Since cTnT has an important role in structurally integrating cardiac troponin I (cTnI) into the thin filaments via its two-way interactions with cTnI and tropomyosin, the present results suggest that R141W mutation in the strong tropomyosin-binding region in cTnT strengthens the integrity of cTnI in the thin filament by stabilizing the interaction between cTnT and tropomyosin, which might allow cTnI to inhibit the thin filament more effectively, leading to a Ca(2+) desensitization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Cardiac troponin T mutation R141W found in dilated cardiomyopathy stabilizes the troponin T-tropomyosin interaction and causes a Ca2+ desensitization.
pubmed:affiliation
Department of Clinical Pharmacology, Kyushu University Graduate School of Medicine, Fukuoka 812-8582, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't