Maximal ATPase activity and calcium sensitivity of reconstituted myofilaments are unaltered by the fetal troponin T re-expressed during human heart failure.
Re-expression of a fetal isoform of troponin T (TnT(4)) has been demonstrated in failing human ventricular myocardium and associated with a decrease in myofibrillar ATPase activity. In order to elucidate the regulatory role of the re-expressed TnT(4) in the failing human heart, we measured ATPase activity in reconstituted cardiac myofilaments prepared with recombinant human TnT(4) or the adult human isoform of troponin T (TnT(3)). Neither the maximal calcium-activated ATPase activity nor the calcium sensitivity of this biochemical assay was significantly different between reconstituted myofilaments containing adult TnT(3) or fetal TnT(4). Our results suggest that the re-expressed fetal TnT(4) is not responsible for the depressed ATPase activity of failing ventricular myofibrils. The increased expression of the fetal isoform of this thin filament regulatory protein in the failing ventricle may be a consequence of a programmed change in gene expression occurring in response to hemodynamic stress, but probably does not contribute to depressed ventricular function characteristic of dilated cardiomyopathies.
Torrealba
Jose R
JR
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, USA.
Lozano
Emilio
E
Griffin
Michael
M
Stoker
Scott
S
McDonald
Kerry
K
Greaser
Marion
M
Wolff
Matthew R
MR
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D020107:Troponin T; D000251:Adenosine Triphosphatases; D002118:Calcium