Differential Regulation of Slow-skeletal and Cardiac Troponin I mRNA during Development and by Thyroid Hormone in Rat Heart

Averyhart-Fullard, Vera; Fraker, Lesa D.; Murphy, Anne M.; Solaro, R J

doi:10.1006/jmcc.1994.1073

Cited by 31 publications

(23 citation statements)

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“…GATA-4 may also mediate effects of thyroid hormone on TnI expression. We had previously demonstrated that neonatal rats that were made hypothyroid had delayed switching of TnI isoforms [39]. Molkentin et al [45] have demonstrated that exogenous thyroid hormone up-regulates GATA-4 DNA-binding activity 3-fold in neonatal cardiocytes, possibly explaining the delay in up-regulation of cardiac TnI mRNA in hypothyroid neonatal rat hearts.…”

Section: Discussionmentioning

confidence: 97%

“…There are E-boxes at positions k435, k380 and k283, and CACCC motifs at positions k690, k470 and k128 on the antisense strand and k73 on the sense strand. Expression of TnI mRNA is influenced by thyroid status in neonatal rat pups [39]. The cardiac TnI mRNA content was approximately twice as high in euthyroid rat pups as in hypothyroid rat pups.…”

Section: Gene Structure and Putative Regulatory Motifsmentioning

confidence: 94%

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Regulation of the rat cardiac troponin I gene by the transcription factor GATA-4

Murphy

Thompson

Peng

et al. 1997

Biochemical Journal

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Troponin I is a thin-filament contractile protein expressed in striated muscle. There are three known troponin I genes which are expressed in a muscle-fibre-type-specific manner in mature animals. Although the slow skeletal troponin I isoform is expressed in fetal and neonatal heart, the cardiac isoform is restricted in its expression to the myocardium at all developmental stages. To study the regulation of this cardiac-specific and developmentally regulated gene in vitro, the rat cardiac troponin I gene was cloned. Transient transfection assays were performed with troponin I–luciferase fusion plasmids to characterize the regulatory regions of the gene. Proximal regions of the upstream sequence were sufficient to support high levels of expression of the reporter gene in cardiocytes and relatively low levels in other cell types. The highest luciferase activity in the cardiocytes was noted with a plasmid that included the region spanning -896 to +45 of the troponin I genomic sequence. Co-transfection of GATA-4, a recently identified cardiac transcription factor, with troponin I–luciferase constructs permitted high levels of luciferase expression in non-cardiac cells. Electrophoretic mobility-shift assays demonstrated specific binding of GATA-4 to oligonucleotides representative of multiple sites of the troponin I sequence. Mutation of a proximal GATA-4 DNA-binding site decreased transcriptional activation in transfected cardiocytes. These results indicate that the proximal cardiac troponin I sequence is sufficient to support high levels of cardiac-specific gene expression and that the GATA-4 transcription factor regulates troponin I–luciferase expression in vitro.

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Section: Discussionmentioning

confidence: 97%

Section: Gene Structure and Putative Regulatory Motifsmentioning

confidence: 94%

Regulation of the rat cardiac troponin I gene by the transcription factor GATA-4

Murphy

Thompson

Peng

et al. 1997

Biochemical Journal

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“…It is interesting to note that while cardiac MHC expression varies with thyroid state, altered levels of triiodothyronine (T×) do not appear to alter the phenotypic expression of other myofibrillar protein isoforms, such as the thin filament proteins troponin I (TnI) and troponin T (TnT) (Averyhart-Fullard et al 1994;Akella et al 1997). However, it is well known that thyroid state markedly affects the Ca¥ handling properties of the sarcoplasmic reticulum (SR) (Kiss et al 1994).…”

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confidence: 99%

Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium

Fitzsimons

Patel

Moss

1998

The Journal of Physiology

106

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The effects of ventricular myosin heavy chain (MHC) composition on the kinetics of activation and relaxation were examined in both chemically skinned and intact myocardial preparations from adult rats. Thyroid deficiency was induced to alter ventricular MHC isoform expression from ∼80 %α‐MHC/20 %β‐MHC in euthyroid rats to 100 %β‐MHC, without altering the expression of thin‐filament‐associated regulatory proteins. In single skinned myocytes, increased expression of β‐MHC did not significantly affect either maximal Ca2+‐activated tension (P0) or the Ca2+ sensitivity of tension (pCa50). However, unloaded shortening velocity (V0) decreased by 80 % due to increased β‐MHC expression. The kinetics of activation and relaxation were examined in skinned multicellular preparations using the caged Ca2+ compound DM‐nitrophen and caged Ca2+ chelator diazo‐2, respectively. Myocardium expressing 100 %β‐MHC exhibited apparent rates of submaximal and maximal tension development (kCa) that were 60 % lower than in control myocardium, and a 2‐fold increase in the half‐time for relaxation from steady‐state submaximal force. The time courses of cell shortening and intracellular Ca2+ transients were assessed in living, electrically paced myocytes, both with and without β‐adrenergic stimulation (70 nm isoproterenol (isoprenaline)). Thyroid deficiency had no affect on either the extent of myocyte shortening or the resting or peak fura‐2 fluorescence ratios. However, induction of β‐MHC expression by thyroid deficiency was associated with increased half‐times for myocyte shortening and relengthening and increased half‐time for the decay of the fura‐2 fluorescence ratio. Qualitatively similar results were obtained in both the absence and the presence of β‐adrenergic stimulation although the β‐agonist accelerated the kinetics of the twitch and the Ca2+ transient. Collectively, these data provide evidence that increased β‐MHC expression contributes significantly to the observed depression of contractile function in thyroid deficient myocardium by slowing the rates of both force development and force relaxation.

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“…Underlined nucleotides represent the location and sequence to which primers were made for use in the reverse transcriptase-polymerase chain reaction experiments. 1994), a hormone shown to influence the TnI isoform switch that occurs in the mammalian neonate heart (Dieckman and Solaro, 1990;Averyhart-Fullard et al, 1994;Huang et al, 2000), raised the possibility that the expression pattern of the genes encoding TnIs and/or TnIc might change in the heart during the metamorphosis of these tadpoles. To test this possibility, we assessed the expression of these genes in the heart of TH-treated Rana tadpoles by northern blot hybridization (results not shown) and, subsequently, by the more sensitive technique of reverse transcriptase-polymerase chain reaction (RT-PCR; Fig.…”

Section: Expression Of the Rana Catesbeiana Genes Encoding Tnic And Tmentioning

confidence: 99%

“…In these organisms, TnIs, the TnI isoform characteristic of slow-twitch muscle fibers, is the predominant TnI isoform within their hearts during embryogenesis and, later in development, is completely replaced by the slightly larger cardiac-specific TnI isoform (TnIc). While the exact factor(s) involved in mediating this developmental switch remains elusive, studies with hyper/hypothyroid rats and transgenic mice (Averyhart-Fullard et al, 1994;Huang et al, 2000) have demonstrated that this switch occurs shortly after birth and have implicated a role for thyroid hormone (TH) in this postembryonic transition.…”

Section: Introductionmentioning

confidence: 99%

Amphibian cardiac troponin I gene's organization, developmental expression, and regulatory properties are different from its mammalian homologue

Warkman

Atkinson

2003

Developmental Dynamics

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In mammals, the expression of the troponin I-slow (TnIs) isoform is predominant in the heart during embryogenesis and, shortly after birth, is replaced by the cardiac-specific isoform, TnIc; a developmental switch thought to be mediated by thyroid hormone. Whereas, in Xenopus, TnIc is expressed at the onset of heart formation and is the only TnI isoform expressed in the heart. Herein, we demonstrate that the expression patterns of these genes appear to be common within the anuran lineage and, unlike their mammalian counterparts, are not affected by thyroid hormone. To elucidate the regulatory mechanism(s) governing the expression of the amphibian TnIc gene, we characterized the TnIc gene from Rana catesbeiana and used its 5 -flanking region to drive expression of green fluorescent protein in the Xenopus transgenic system. Our results demonstrate that a 300-bp minimal promoter containing intact GATA and CArG-box elements is sufficient to drive expression of this reporter gene in a pattern that mimics, both spatially and temporally, the expression of the endogenous Xenopus TnIc gene. Developmental Dynamics 229:275-288, 2004.

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Differential Regulation of Slow-skeletal and Cardiac Troponin I mRNA during Development and by Thyroid Hormone in Rat Heart

Cited by 31 publications

References 0 publications

Regulation of the rat cardiac troponin I gene by the transcription factor GATA-4

Regulation of the rat cardiac troponin I gene by the transcription factor GATA-4

Role of myosin heavy chain composition in kinetics of force development and relaxation in rat myocardium

Amphibian cardiac troponin I gene's organization, developmental expression, and regulatory properties are different from its mammalian homologue

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