Analysis of the rat connexin 43 proximal promoter in neonatal cardiomyocytes

Teunissen, Birgit E.J.; Jansen, Anita; Amersfoorth, Shirley C.M. van; O’Brien, Terrence X.; Jongsma, Habo J.; Bierhuizen, Marti F.A.

doi:10.1016/j.gene.2003.08.011

Cited by 45 publications

(45 citation statements)

References 35 publications

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“…Similar to the hearts of the Nkx2.5 transgenic mice (Transgenic mice models), neonatal cardiomyocytes, in which Nkx2.5 is over expressed by adenoviral infection, display dramatically reduced levels of Cx43 protein and mRNA. 70,73 In addition, Nkx2.5 over expression also elicited an approximately 2-fold drop in Cx43 proximal promoter activity, although this does not fully explain the severe drop in Cx43 mRNA. Presumably, additional transcription factors, repressor sites or other molecular mechanisms are necessary for the down-regulation of Cx43 in neonatal cardiomyocytes.…”

Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 97%

“…Heterogeneity indicates a heterogeneous distribution of Cx43 throughout the ventricles. Nkx2.5 overexpression fl fl Also a 2-fold drop in Cx43 proximal promoter activity 70,73 Abbreviations: NCM, neonatal cardiomyocytes; JNK, c-Jun N-terminal kinase; ›, up-regulated; fl, down-regulated; $, unaltered.…”

Section: Transgenic Mice Modelsmentioning

confidence: 99%

“…The effects of hypertrophic stimuli, 71 signal transduction molecules, 56,72 and transcription factors, 70,73 known to be involved in hypertrophic signalling, on myocardial connexin expression have been investigated in cultured neonatal cardiomyocytes (Table 5).…”

Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 99%

“…However, AP1 has been shown to be necessary for activation of the Cx43 proximal promoter in neonatal ventricular myocytes. 73 The molecular mechanism behind this apparent discrepancy still needs to be elucidated. Most likely additional, post-transcriptional mechanisms are involved in JNK-mediated down-regulation of Cx43 as well, because of the near 90% reduction in protein compared with the 40% reduction in mRNA.…”

Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 99%

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Regulation of myocardial connexins during hypertrophic remodelling

Teunissen

Jongsma

Bierhuizen

2004

European Heart Journal

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Cardiac hypertrophic remodelling, initiated by signalling cascades in response to increased workload, injury or intrinsic disease, is initially adaptive. However, prolonged hypertrophy as a consequence of pathological stress leads to maladaptive changes that increase the risk for fatal ventricular arrhythmias. One of these changes is the remodelling of myocardial gap junctions, which provide for electrical coupling of adjacent cardiomyocytes. Myocardial gap junctions are composed of three connexin isotypes, connexin40 (Cx40), -43 (Cx43), and -45 (Cx45) and each display a characteristic developmental and regional expression pattern. Alterations in the distribution and expression of Cx43, the predominant isoform in the adult ventricles, has been the main focus of examination in humans, experimental animal models and cultured cardiomyocytes in response to hypertrophy. The molecular mechanisms and signalling pathways underlying these changes have been studied less thoroughly. In this review we summarize what is known about the remodelling of myocardial gap junctions during hypertrophy, the putative underlying mechanisms and functional consequences thereof.

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Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 97%

Section: Transgenic Mice Modelsmentioning

confidence: 99%

Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 99%

Section: Biochemical Inducers Of Connexin Remodelling In Cardiomyocytesmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of myocardial connexins during hypertrophic remodelling

Teunissen

Jongsma

Bierhuizen

2004

European Heart Journal

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“…7). Both the endogenous level of Nkx2.5 protein and the endogenous Gata4 activity were reported to be very low in cultured newborn rat myocytes (70,71). We transfected newborn rat myocytes in culture with a reporter construct, including a sequence from the Ifi204 gene 5Ј-flanking segment (shown in Fig.…”

Section: The Expression Of the Ifi204 Gene Could Be Synergistically Tmentioning

confidence: 99%

p204 Is Required for the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes

Ding

Liu

Huang

et al. 2006

Journal of Biological Chemistry

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Among 10 adult mouse tissues tested, the p204 protein levels were highest in heart and skeletal muscle.We described previously that the MyoD-inducible p204 protein is required for the differentiation of cultured murine C2C12 skeletal muscle myoblasts to myotubes. Here we report that p204 was also required for the differentiation of cultured P19 murine embryonal carcinoma stem cells to beating cardiac myocytes. As shown by others, this process can be triggered by dimethyl sulfoxide (DMSO). We established that DMSO induced the formation of 204RNA and p204. Ectopic p204 could partially substitute for DMSO in inducing differentiation, whereas ectopic 204 antisense RNA inhibited the differentiation. Experiments with reporter constructs, including regulatory regions from the Ifi204 gene (encoding p204) in P19 cells and in cultured newborn rat cardiac myocytes, as well as chromatin coimmunoprecipitations with transcription factors, revealed that p204 expression was synergistically transactivated by the cardiac Gata4, Nkx2.5, and Tbx5 transcription factors. Furthermore, ectopic p204 triggered the expression of Gata4 and Nkx2.5 in P19 cells. p204 contains a nuclear export signal and was partially translocated to the cytoplasm during the differentiation. p204 from which the nuclear export signal was deleted was not translocated, and it did not induce differentiation The interferons are vertebrate cytokines with antimicrobial, cell growth regulatory, and immunomodulatory activities that also affect differentiation (1-3). They function by modulating the expression of many genes, including those of the gene 200 cluster (4 -10). In the mouse this cluster consists of at least 10 genes, which encode the p200 family proteins (11). The human counterpart of the cluster is smaller; it consists apparently of only four genes (MNDA, IFI16, AIM2, and IFIX) that encode the Hin200 family proteins (12-15).Among the two best characterized members of the murine p200 family proteins is p202a (which was designated earlier as p202) (16 -26). p202a modulates transcription, cell proliferation, and apoptosis. It functions primarily by binding various sequence-specific transcription factors and inhibiting their activity generally, but not exclusively, by binding them and blocking their sequence-specific binding to DNA (24). p202a overexpression was implicated in the susceptibility of mice to the autoimmune disease lupus (27).The other much studied p200 family protein p204 is encoded by the Ifi204 gene (5). p204 is structurally related to p202a and is inducible by interferons, as is p202a. Depending on the cell type and the state of differentiation, p204 can be located in the nucleolus, the nucleoplasm, or the cytoplasm (28 -30). Its overexpression in cultured mammalian cells is growth-inhibitory (28, 31). It can delay the progression of cells from the G 0 /G 1 to the S phase of the cell cycle (31). p204 can inhibit the transcription of ribosomal RNA by binding to the ribosomal DNAspecific UBF transcription factor and by inhibiting its binding to D...

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Gap Junctions

Nielsen,

Nygaard Axelsen,

Sorgen

et al. 2012

Comprehensive Physiology

381

365

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Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell‐cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981‐2035, 2012.

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Analysis of the rat connexin 43 proximal promoter in neonatal cardiomyocytes

Cited by 45 publications

References 35 publications

Regulation of myocardial connexins during hypertrophic remodelling

Regulation of myocardial connexins during hypertrophic remodelling

p204 Is Required for the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes

Gap Junctions

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