TY - JOUR
T1 - Troponin T mRNA and protein isoforms in the human left ventricle
T2 - Pattern of expression in failing and control hearts
AU - Mesnard-Rouiller, Laurence
AU - Mercadier, Jean Jacques
AU - Butler-Browne, Gillian
AU - Heimburger, Michele
AU - Logeart, Damien
AU - Allen, Paul D.
AU - Samson, Françoise
PY - 1997/11
Y1 - 1997/11
N2 - We and others have previously cloned several cDNAs of human cardiac troponin T (cTnT), demonstrating the multiplicity of cTnT isoforms in the human heart. Four of them named cTnT1, 2, 3 and 4 result from a combinatorial alternative inclusion of 30- and 15-nucleotides in the 5' coding region of the cDNAs. In failing human ventricles, increased expression of cTnT4 has been reported at the protein level. More recent RT-PCR experiments showed increased expression of fetal-type splicing products in the 5' region, one of them corresponding to cTnT1. To clarify this issue, we examined the accumulation of the 4 cTnT mRNA and protein species in left ventricular specimens at the time of heart transplantation, and in control left ventricular samples using RNase protection and Western blotting. In all samples, cTnT3 was the major mRNA isoform, cTnT4 a minor isoform while cTnT1 and cTnT2 mRNAs were present but barely detectable. At the protein level, cTnT3, 4 and 1 were detected with the same relative abundance as that seen at the mRNA level. In addition, we detected a fourth TnT species of very low abundance corresponding either to a skeletal or to a 'short' cardiac TNT isoform. Compared to controls, increased levels of cTnT4 mRNA and protein were detected in only half the failing ventricles independently of the cause of failure, suggesting that this increase map not be a general characteristic of left ventricular failure but instead could be related to stress. Unexpectedly, we found a decrease in cTnT1 protein expression in all failing ventricular samples studied, compared to controls.
AB - We and others have previously cloned several cDNAs of human cardiac troponin T (cTnT), demonstrating the multiplicity of cTnT isoforms in the human heart. Four of them named cTnT1, 2, 3 and 4 result from a combinatorial alternative inclusion of 30- and 15-nucleotides in the 5' coding region of the cDNAs. In failing human ventricles, increased expression of cTnT4 has been reported at the protein level. More recent RT-PCR experiments showed increased expression of fetal-type splicing products in the 5' region, one of them corresponding to cTnT1. To clarify this issue, we examined the accumulation of the 4 cTnT mRNA and protein species in left ventricular specimens at the time of heart transplantation, and in control left ventricular samples using RNase protection and Western blotting. In all samples, cTnT3 was the major mRNA isoform, cTnT4 a minor isoform while cTnT1 and cTnT2 mRNAs were present but barely detectable. At the protein level, cTnT3, 4 and 1 were detected with the same relative abundance as that seen at the mRNA level. In addition, we detected a fourth TnT species of very low abundance corresponding either to a skeletal or to a 'short' cardiac TNT isoform. Compared to controls, increased levels of cTnT4 mRNA and protein were detected in only half the failing ventricles independently of the cause of failure, suggesting that this increase map not be a general characteristic of left ventricular failure but instead could be related to stress. Unexpectedly, we found a decrease in cTnT1 protein expression in all failing ventricular samples studied, compared to controls.
KW - Gene expression
KW - Heart failure
KW - Human heart
KW - Stress
KW - Troponin T
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U2 - 10.1006/jmcc.1997.0519
DO - 10.1006/jmcc.1997.0519
M3 - Article
C2 - 9405179
AN - SCOPUS:0031282110
VL - 29
SP - 3043
EP - 3055
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 11
ER -