Endothelin-1 Stimulates the Expression of L-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes via the Extracellular Signal–Regulated Kinase 1/2 Pathway

Yu, Liangzhu; Li, Mincai; She, Tonghui; Shi, Chunrong; Meng, Wei; Bang-hua, Wang; Cheng, Maojie

doi:10.1007/s00232-013-9538-7

Cited by 9 publications

(4 citation statements)

References 55 publications

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“…It has been shown that nuclear factor-kappaB (NFκB) stimulates functional CaV1.2 expression in cerebral artery myocytes [10]. Endothelin-1 stimulation increases the LTCC CaV1.2 transcription in cardiomyocytes via activation of extracellular signal-regulated kinase 1/2 pathway [11]. Our present study demonstrated that Myocardin regulated transcriptional activity of LTCC CaV1.2 via binding to CArG boxes.…”

Section: Discussionsupporting

confidence: 56%

Construction and Functional Analysis of Luciferase Reporter Plasmid Containing CaV1.2 Gene Promoter

Li¹,

Gong²,

Zhang³

et al. 2016

Proceedings of the 2015 International Conference on Materials Chemistry and Environmental Protection (Meep-15)

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L-type Ca 2+ channels (LTCCs) are the main mediators of Ca 2+ influx. LTCCs are multi-subunit complexes, of which CaV1.2 subunit forms the channel pore for Ca 2+ movement. Ca 2+ influx through LTCC CaV1.2 is a proximal signal for pathological cardiomyocyte hypertrophy. However, very little is known regarding the molecular mechanism of LTCC transcription regulation. Myocardin, a co-activator of serum response factor (SRF) that potently transactivates CArG box-containing cardiac and smooth muscle target genes, can stimulate neonatal rat cardiomyocyte hypertrophy. In the present study, the gene fragment of rat LTCC CaV1.2 promoter containing five CArG boxes or no CArG box was amplified by PCR and cloned into empty vector pGL3-Basic to construct luciferase reporter plasmids, then luciferase activity assay was performed in HEK293T cells. The results showed that the luciferase reporter plasmids were constructed successfully, Myocardin potently activated CArG boxcontaining LTCC CaV1.2 reporter, by contrast, Myocardin had a weaker transcriptional activation on LTCC CaV1.2 reporter containing no CArG box. The results suggest that Myocardin may play a critical role in regulating the expression of LTCC CaV1.2 in cardiomyocyte hypertrophy.

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Section: Discussionsupporting

confidence: 56%

Construction and Functional Analysis of Luciferase Reporter Plasmid Containing CaV1.2 Gene Promoter

Li¹,

Gong²,

Zhang³

et al. 2016

Proceedings of the 2015 International Conference on Materials Chemistry and Environmental Protection (Meep-15)

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“…ET-1 acts in a paracrine and/or autocrine fashion and therefore tissue concentrations are significantly higher than those in the circulation 29. The concentration of ET-1 (10 nM) was chosen based on other studies 30-33 and the rationale that ET-1 levels in the local tissue are much greater than in circulation. In the present study, we found that fetal rat cardiomyocytes exposed to elevated levels of ET-1 exhibited both increased binucleation and decreased proliferation.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 Promotes Cardiomyocyte Terminal Differentiation in the Developing Heart via Heightened DNA Methylation

Paradis¹,

Xiao²,

Zhou³

et al. 2014

Int. J. Med. Sci.

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Aims: Hypoxia is a major stress on fetal development and leads to induction of endothelin-1 (ET-1) expression. We tested the hypothesis that ET-1 stimulates the terminal differentiation of cardiomyocytes from mononucleate to binucleate in the developing heart.Methods and results: Hypoxia (10.5% O2) treatment of pregnant rats from day 15 to day 21 resulted in a significant increase in prepro-ET-1 mRNA expression in fetal hearts. ET-1 ex vivo treatment of fetal rat cardiomyocytes increased percent binucleate cells and decreased Ki-67 expression, a marker for proliferation, under both control and hypoxic conditions. Hypoxia alone decreased Ki-67 expression and in conjunction with ET-1 treatment decreased cardiomyocyte size. PD145065, a non-selective ET-receptor antagonist, blocked the changes in binucleation and proliferation caused by ET-1. DNA methylation in fetal cardiomyocytes was significantly increased with ET-1 treatment, which was blocked by 5-aza-2'-deoxycytidine, a DNA methylation inhibitor. In addition, 5-aza-2'-deoxycytidine treatment abrogated the increase in binucleation and decrease in proliferation induced by ET-1.Conclusions: Hypoxic stress and synthesis of ET-1 increases DNA methylation and promotes terminal differentiation of cardiomyocytes in the developing heart. This premature exit of the cell cycle may lead to a reduced cardiomyocyte endowment in the heart and have a negative impact on cardiac function.

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“…In addition, cardiac fibroblasts (CFs), are also affected by mechanical stimulation, demonstrating changes in migration [77], ECM expression [78], differentiation, and myofibroblast activation [79–83] following Rho/ROCK activation. MAPK and ERK activation can mediate hypertrophy [84–92], calcium handling [93], oxidative stress [94–97], remodeling [98], proliferation [99], apoptosis [100–105], and maturation in CMs [106–108]. CF response to oxidative stress [109] is also mediated by MAPK and ERK activation.…”

Section: Biological Basis For Mechanical Stimulationmentioning

confidence: 99%

Electrical and mechanical stimulation of cardiac cells and tissue constructs

Stoppel

Kaplan

Black

2016

Advanced Drug Delivery Reviews

224

190

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The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro.

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Endothelin-1 Stimulates the Expression of L-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes via the Extracellular Signal–Regulated Kinase 1/2 Pathway

Cited by 9 publications

References 55 publications

Construction and Functional Analysis of Luciferase Reporter Plasmid Containing CaV1.2 Gene Promoter

Construction and Functional Analysis of Luciferase Reporter Plasmid Containing CaV1.2 Gene Promoter

Endothelin-1 Promotes Cardiomyocyte Terminal Differentiation in the Developing Heart via Heightened DNA Methylation

Electrical and mechanical stimulation of cardiac cells and tissue constructs

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