Myosin light chain composition in non-failing donor and end-stage failing human ventricular myocardium.
The increased Ca(2+)-responsiveness in end-stage human heart failure cannot be attributed to contractile protein isoform changes, but rather is the complex resultant of changes in degree of phosphorylation of VLC-2 and TnI. Despite the decreased basal level of VLC-2 phosphorylation the response to VLC-2 dephosphorylation is enhanced in failing myocytes, which might result from differences in endogenous phosphorylation of thin and thick filament proteins between donor and failing hearts. Taken together decreased VLC-2 phosphorylation in end-stage human heart failure might represent a compensatory process leading to an improvement of myocardial contractility by opposing the detrimental effects of increased Ca(2+)-responsiveness of force and impaired Ca(2+)-handling on diastolic function.
van der Velden
J
J
Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.
Papp
Z
Z
Boontje
N M
NM
Zaremba
R
R
de Jong
J W
JW
Janssen
P M L
PM
Hasenfuss
G
G
Stienen
G J M
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D009206:Myocardium / Q000166:cytology*; D018994:Myosin Light Chains / Q000737:chemistry*; D010766:Phosphorylation; D020033:Protein Isoforms; D011720:Pyrazoles / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D018994:Myosin Light Chains; D020033:Protein Isoforms; D011720:Pyrazoles; D011743:Pyrimidines; D002118:Calcium