Epigenetic regulation of phosphodiesterase 4d in restrictive cardiomyopathy mice with cTnI mutations

Zhao, Weian; Wu, Xiaoqi; Wang, Zhiyuan; Pan, Bo; Liu, Lifei; Liu, Lingjuan; Huang, Xupei; Tian, Jie

doi:10.1007/s11427-018-9463-9

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…Moreover, their prediction that mutations in thin filament proteins may alter nuclear function has been demonstrated by Wu et al (2015) , who reported that altered adrenergic control of contractility in a TNNT2 DCM (cTnT-R173W) mutation occurred because of the mutant cTnT entering the nucleus and epigenetically upregulating phosphodiesterase genes. Similar results were obtained in a restrictive cardiomyopathy mutation in which a mutant nuclear cTnI interacted with histone deacetylase 1, inducing down-regulation of phosphodiesterase-4 ( Zhao et al, 2020 ).…”

Section: Challenges and Future Directionssupporting

confidence: 73%

Novel insights into sarcomere regulatory systems control of cardiac thin filament activation

Solı́s

Solaro

2021

Journal of General Physiology

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Our review focuses on sarcomere regulatory mechanisms with a discussion of cardiac-specific modifications to the three-state model of thin filament activation from a blocked to closed to open state. We discuss modulation of these thin filament transitions by Ca2+, by crossbridge interactions, and by thick filament–associated proteins, cardiac myosin–binding protein C (cMyBP-C), cardiac regulatory light chain (cRLC), and titin. Emerging evidence supports the idea that the cooperative activation of the thin filaments despite a single Ca2+ triggering regulatory site on troponin C (cTnC) cannot be considered in isolation of other functional domains of the sarcomere. We discuss long- and short-range interactions among these domains with the regulatory units of thin filaments, including proteins at the barbed end at the Z-disc and the pointed end near the M-band. Important to these discussions is the ever-increasing understanding of the role of cMyBP-C, cRLC, and titin filaments. Detailed knowledge of these control processes is critical to the understanding of mechanisms sustaining physiological cardiac state with varying hemodynamic load, to better defining genetic and acquired cardiac disorders, and to developing targets for therapies at the level of the sarcomeres.

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Section: Challenges and Future Directionssupporting

confidence: 73%

Novel insights into sarcomere regulatory systems control of cardiac thin filament activation

Solı́s

Solaro

2021

Journal of General Physiology

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“…Moreover, an increase in binding of the histone transmethylase SMYD1 and histone deacetylase HDAC1 was observed in the promoter region of mutated cTnI. The overall findings of this study indicated that the decrease in PDE4d in RCM mice as a result of cTnI mutations could be regulated by a balance between histone acetylation and methylation [56]. cTnI is a subunit of the thin filament involved in regulation of heart contraction; mutations in cTnI have been shown to be most prevalently associated with RCM.…”

Section: Histone Modifications In Rcmmentioning

confidence: 56%

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

Pagiatakis

Mauro

2021

IJMS

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Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders.

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“…Western blotting was performed as detailed in the previous study [28]. Proteins bound to the PDVF (polyvinylidene fluoride) membrane were incubated with primary antibodies against CBP (Abcam, Cambridge, UK), p300 (Abcam), GAPDH (Arigo, China), caspase-3 (CST, Boston, MA, USA), cleaved caspase-3 (CST), caspase-9 (CST), cleaved caspase-9 (CST), acH3 (CST), H3 (CST) and JNK (CST).…”

Section: Western Blottingmentioning

confidence: 99%

Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Yang

Chen

et al. 2021

Korean J Physiol Pharmacol

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Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

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Epigenetic regulation of phosphodiesterase 4d in restrictive cardiomyopathy mice with cTnI mutations

Cited by 16 publications

References 30 publications

Novel insights into sarcomere regulatory systems control of cardiac thin filament activation

Novel insights into sarcomere regulatory systems control of cardiac thin filament activation

The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

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