rdf:type |
|
lifeskim:mentions |
umls-concept:C0027061,
umls-concept:C0031715,
umls-concept:C0033621,
umls-concept:C0036667,
umls-concept:C0041199,
umls-concept:C0086418,
umls-concept:C0242210,
umls-concept:C0256371,
umls-concept:C0312418,
umls-concept:C0392756,
umls-concept:C0439098,
umls-concept:C0596235,
umls-concept:C1149266
|
pubmed:issue |
2
|
pubmed:dateCreated |
2010-1-19
|
pubmed:abstractText |
Previous studies indicated that the increase in protein kinase C (PKC)-mediated myofilament protein phosphorylation observed in failing myocardium might be detrimental for contractile function. This study was designed to reveal and compare the effects of PKCalpha- and PKCepsilon-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different [Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCalpha and PKCepsilon equally reduced Ca2+ sensitivity in failing cardiomyocytes (DeltapCa50 = 0.08 +/- 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C) in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of protein kinase A (PKA) resulted in a further reduction in Ca2+ sensitivity, indicating that the effects of both PKC isoforms were not caused by cross-phosphorylation of PKA sites. Both isozymes showed no effects on maximal force and only PKCalpha resulted in a modest significant reduction in passive force. Effects of PKCalpha were only minor in donor cardiomyocytes, presumably because of already saturated cTnI and cMyBP-C phosphorylation levels. Donor tissue could therefore be used as a tool to reveal the functional effects of troponin T (cTnT) phosphorylation by PKCalpha. Massive dephosphorylation of cTnT with alkaline phosphatase increased Ca2+ sensitivity. Subsequently, PKCalpha treatment of donor cardiomyocytes reduced Ca2+ sensitivity (DeltapCa50 = 0.08 +/- 0.02) and solely increased phosphorylation of cTnT, but did not affect maximal and passive force. PKCalpha- and PKCepsilon-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19655190-10536002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19655190-11179042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19655190-12065321,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19655190-9918525
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
1435-1803
|
pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
105
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
289-300
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19655190-Adolescent,
pubmed-meshheading:19655190-Adult,
pubmed-meshheading:19655190-Calcium,
pubmed-meshheading:19655190-Carrier Proteins,
pubmed-meshheading:19655190-Cells, Cultured,
pubmed-meshheading:19655190-Female,
pubmed-meshheading:19655190-Heart Failure,
pubmed-meshheading:19655190-Humans,
pubmed-meshheading:19655190-Male,
pubmed-meshheading:19655190-Middle Aged,
pubmed-meshheading:19655190-Myocardium,
pubmed-meshheading:19655190-Phosphorylation,
pubmed-meshheading:19655190-Protein Kinase C-alpha,
pubmed-meshheading:19655190-Protein Kinase C-epsilon,
pubmed-meshheading:19655190-Troponin I,
pubmed-meshheading:19655190-Troponin T,
pubmed-meshheading:19655190-Young Adult
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pubmed:year |
2010
|