Early growth response 1 is an early signal inducing Cav3.2 T-type calcium channels during cardiac hypertrophy

Hsu, Shao-Chun; Chang, Yao-Tang; Chen, Chien‐Chang

doi:10.1093/cvr/cvt190

Cited by 16 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hallmarks of pathologic changes of DCM include cardiomyocyte hypertrophy and cardiac fibrosis (20). Current evidence suggests that Smad3, GATA4 and EGR1 are the critical factors in regulating cardiomyocyte hypertrophy and cardiac fibrosis (41)(42)(43)(44)(45)(46)). An array of cardiac genes, including atrial natriuretic peptide, brain natriuretic peptide, α-myosin heavy chain and β-myosin heavy chain, are regulated by GATA4 in response to hypertrophic agonists (42).…”

Section: Discussionmentioning

confidence: 99%

“…Isoproterenol and phenylephrine infusion-induced cardiac hypertrophy and fibrosis were alleviated by EGR1 deficiency in mice (45). Hsu et al demonstrated that phenylephrine-induced neonatal rat ventricular myocyte and H9c2 cell hypertrophy was prevented by EGR1 knockdown via regulating Ca v 3.2 expression (43). Similarly, Smad3 knockout mice displayed attenuated cardiac remodeling in response to angiotensin II stimulation (46).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Jiang

Yi²,

et al. 2017

Mol Med

View full text Add to dashboard Cite

Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM), while the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families, in DCM are unclear. To this end, 12 normal and 15 DCM heart samples were included in the present study. A murine cardiac remodeling model was induced by transverse aortic constriction (TAC). Real-time polymerase chain reaction was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated with TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end diastolic diameter and left ventricular ejection fraction. However, there was no obvious change in the expression levels of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A and SETD1B) between control and DCM hearts or remodeled mouse hearts. Furthermore, the dimethylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4 and EGR1, which might be regulated by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role in the pathological processes of DCM by regulating H3K4me2 and the expression of Smad3, GATA4 and EGR1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Jiang

Yi²,

et al. 2017

Mol Med

View full text Add to dashboard Cite

show abstract

“…Although activation and deactivation of T-type Ca 2ϩ channel gene expression has been observed in many pathological conditions and under various stimuli (4, 26, 35), transcription factors involved in such gene regulation are just beginning to emerge. For instance, repressor element-1 silencing transcription factor, also known as neuron-restrictive silencer factor (15,36), early growth response factor-1 (ERG1) (12), transcription factor GATA4 (28), cardiac homeobox transcription factor Csx/Nkx2.5 (38), and LEF1/␤-catenin complex (39) have been reported to function as a transcriptional regulator of ␣ 1H . However, it is of note that, among these identified transcription factors, ERG1, GATA4, NKX2.5, as well as ␤-catenin signaling have been reported to be regulated by hypoxia (13,25,28,41).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of α_1H T-type calcium channel under hypoxia

Hassan

Zhou

Liu

et al. 2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

scriptional regulation of ␣1H T-type calcium channel under hypoxia. Am J Physiol Cell Physiol 307: C648 -C656, 2014. First published August 6, 2014; doi:10.1152/ajpcell.00210.2014.-The low-voltageactivated T-type Ca 2ϩ channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, ␣1G, ␣1H, and ␣1I, only ␣1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of ␣1G and ␣1H gene promoters with the aim to identify the functional hypoxia-response elements (HREs). In rat pulmonary artery smooth muscle cells (PASMCs) and pheochromocytoma (PC12) cells after hypoxia (3% O2) exposure, we observed a prominent increase in ␣ 1H mRNA at 12 h along with a significant rise in ␣ 1H-mediated T-type current at 24 and 48 h. We then cloned two promoter fragments from the 5=-flanking regions of rat ␣ 1G and ␣1H gene, 2,000 and 3,076 bp, respectively, and inserted these fragments into a luciferase reporter vector. Transient transfection of PASMCs and PC12 cells with these recombinant constructs and subsequent luciferase assay revealed a significant increase in luciferase activity from the reporter containing the ␣1H, but not ␣1G, promoter fragment under hypoxia. Using serial deletion and point mutation analysis strategies, we identified a functional HRE at site Ϫ1,173CACGCϪ1,169 within the ␣ 1H promoter region. Furthermore, an electrophoretic mobility shift assay using this site as a DNA probe demonstrated an increased binding activity to nuclear protein extracts from the cells after hypoxia exposure. Taken together, these findings indicate that hypoxia-induced ␣ 1H upregulation involves binding of hypoxia-inducible factor to an HRE within the ␣1H promoter region.T-type calcium channel; gene expression; hypoxia; hypoxia-response element HYPOXIA IS AN ESSENTIAL and critical pathological component of many pulmonary disorders, including acute lung injury, chronic obstructive pulmonary disease, and pulmonary hypertension. One of the most important responses to hypoxia in the pulmonary vasculature is a change in intracellular calcium homeostasis. Smooth muscle cells in pulmonary arteries, i.e., pulmonary artery smooth muscle cells (PASMCs), and endothelial cell in the microvessels, i.e., pulmonary microvascular endothelial cells (PMVECs), are both equipped with voltage-gated Ca 2ϩ channels. The two major classes of voltage-gated Ca 2ϩ channels are differentiated by their electrophysiological properties: high-voltage-activated channels, which include the L-, N-, P/Q-, and R-subtypes, and low-voltage-activated channels, also known as T-type channels. In addition to their distinct voltage dependence of activation, T-type channels also exhibit a unique rapid inactivation and slow deactivation time course (29). Functionally, the L-type channel has long been considered the predominant source of C...

show abstract

“…(Harraz et al, 2015) T-type calcium channel activity has also been linked to gene transcription. Activation of T-type channels has been shown to activate nuclear factor of activated T cells in cartilage tissue (Lin et al, 2014) and during the development of cardiac hypertrophy (Hsu et al, 2013;Huang et al, 2013a). T-type channels have also been linked to activation of CREB in cardiomyocytes in response to aldosterone .…”

Section: B Physiologic Roles Of Ca V 3 Calcium Channelsmentioning

confidence: 99%

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Zamponi¹,

Striessnig²,

Koschak³

et al. 2015

Pharmacol Rev

903

992

View full text Add to dashboard Cite

Early growth response 1 is an early signal inducing Cav3.2 T-type calcium channels during cardiac hypertrophy

Abstract: Cav3.2 is induced early by Egr1 during cardiac hypertrophy and Cav3.2 is an important mediator of Egr1 in regulating cardiac hypertrophy.

Cited by 16 publications

References 35 publications

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Transcriptional regulation of α_1H T-type calcium channel under hypoxia

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Contact Info

Product

Resources

About

Early growth response 1 is an early signal inducing Cav3.2 T-type calcium channels during cardiac hypertrophy

Abstract: Cav3.2 is induced early by Egr1 during cardiac hypertrophy and Cav3.2 is an important mediator of Egr1 in regulating cardiac hypertrophy.

Cited by 16 publications

References 35 publications

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Transcriptional regulation of α1H T-type calcium channel under hypoxia

The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

Contact Info

Product

Resources

About

Transcriptional regulation of α_1H T-type calcium channel under hypoxia