Linked Life Data

11735257

Source:http://linkedlifedata.com/resource/pubmed/id/11735257

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-12-12
pubmed:abstractText
Functional consequences of the six mutations (R145G, R145Q, R162W, DeltaK183, G203S, K206Q) in cardiac troponin I (cTnI) that cause familial hypertrophic cardiomyopathy (HCM) were studied using purified recombinant human cTnI. The missense mutations R145G and R145Q in the inhibitory region of cTnI reduced the intrinsic inhibitory activity of cTnI without changing the apparent affinity for actin. On the other hand, the missense mutation R162W in the second troponin C binding region and the deletion mutation DeltaK183 near the second actin-tropomyosin region reduced the apparent affinity of cTnI for actin without changing the intrinsic inhibitory activity. Ca(2+) titration of a fluorescent probe-labeled human cardiac troponin C (cTnC) showed that only R162W mutation impaired the cTnC-cTnI interaction determining the Ca(2+) affinity of the N-terminal regulatory domain of cTnC. Exchanging the human cardiac troponin into isolated cardiac myofibrils or skinned cardiac muscle fibers showed that the mutations R145G, R145Q, R162W, DeltaK183 and K206Q induced a definite increase in the Ca(2+)-sensitivity of myofibrillar ATPase activity and force generation in skinned muscle fibers. Although the mutation G203S also showed a tendency to increase the Ca(2+) sensitivity in both myofibrils and skinned muscle fibers, no statistically significant difference compared with wild-type cTnI could be detected. These results demonstrated that most of the HCM-linked cTnI mutations did affect the regulatory processes involving the cTnI molecule, and that at least five mutations (R145G, R145Q, R162W, DeltaK183, K206Q) increased the Ca(2+) sensitivity of cardiac muscle contraction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2095-107
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Functional consequences of the mutations in human cardiac troponin I gene found in familial hypertrophic cardiomyopathy.
pubmed:affiliation
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. yanaga@clipharm.med.kyushu-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't