Thyroid hormone inhibits slow skeletal TnI expression in cardiac TnI-null myocardial cells.
A cardiac troponin I (cTnI) gene knockout mouse model has been created and the phenotype of the cTnI null mice is an acute heart failure resulting from the deficiency of TnI and a diastolic dysfunction. Two isoforms of TnI (the fetal form ssTnI and the adult form cTnI) are mainly expressed in the heart under a developmentally regulated program. In our previous studies, we demonstrated that thyroid hormone could alter the time course of ssTnI gene expression in the heart. In the present study, we have successfully cultured neonatal cardiac myocytes from wild type and cTnI null mouse hearts. The ssTnI gene expression pattern has been investigated in these cells. By using Western blotting assays, a TnI isoform switching has been observed in the wild type cardiac myocytes. The pattern of TnI isoform switching is very similar to that of in vivo study we reported previously. In cTnI null cardiac myocytes cultured from day 1 to day 7, there is a continuous decline in ssTnI concentration in the cells. The time course of ssTnI decline in cTnI null cells is similar to that of wild type cardiac myocytes, suggesting that there is no significant compensation of ssTnI gene expression for the absence of the cTnI. This observation is different from what we found previously at a whole heart level. In addition, when thyroid hormone T3 (20 ng/ml) is added to cultured cTnI null cardiac myocytes, the decline of ssTnI concentration occurs earlier. This is inconsistent with our observations from previous in vivo studies. The data demonstrate that thyroid hormone can alter the time course of ssTnI gene expression in cultured cardiac myocytes and TnI gene regulation is also controlled by some unknown programmed events inside of cardiac myocytes.
Riedel
Beth
B
Department of Biomedical Science and Center for Molecular Biology and Biotechnology, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
Jia
Yuanyuan
Y
Du
Jianfeng
J
Akerman
Sarah
S
Huang
Xupei
X
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D014284:Triiodothyronine / Q000502:physiology*; D019210:Troponin I / Q000096:biosynthesis*
D019210:Troponin I; D014284:Triiodothyronine