SIRT1 deacetylates the cardiac transcription factor Nkx2.5 and inhibits its transcriptional activity

Tang, Xiaoqiang; Ma, Han; Han, Lei; Zheng, Wei; Lu, Yuanyao; Chen, Xiaofeng; Liang, Shu Ting; Wei, Gong Hong; Zhang, Zhu Qin; Chen, Hou-Zao; Liu, De-Pei

doi:10.1038/srep36576

Cited by 29 publications

(18 citation statements)

References 32 publications

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“…The Sirtuins are NAD + -dependent regulators of cellular metabolism and senescence. SIRT1, SIRT2, SIRT3, SIRT6, and SIRT7 are reported to regulate cardiac aging (13,(55)(56)(57)(58)(59). SIRT2 targets the Liver kinase B1 (LKB1)-AMPK signaling to regulate energetic metabolic and hypertrophic growth of cardiomyocytes in aged mice (53).…”

Section: The Regulation Of Metabolism Dysfunction On Cardiomyocyte Sementioning

confidence: 99%

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments

2020

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Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis). These events eventually lead to cardiac remodeling and failure. Senescent cardiomyocytes show the hallmarks of DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile dysfunction, hypertrophic growth, and senescence-associated secreting phenotype (SASP). Metabolism within cardiomyocytes is essential not only to fuel the pump function of the heart but also to maintain the functional homeostasis and participate in the senescence of cardiomyocytes. The senescence of cardiomyocyte is also regulated by the non-myocytes (endothelial cells, fibroblasts, and immune cells) in the local microenvironment. On the other hand, the senescent cardiomyocytes alter their phenotypes and subsequently affect the non-myocytes in the local microenvironment and contribute to cardiac aging and pathological remodeling. In this review, we first summarized the hallmarks of the senescence of cardiomyocytes. Then, we discussed the metabolic switch within senescent cardiomyocytes and provided a discussion of the cellular communications between dysfunctional cardiomyocytes and non-myocytes in the local microenvironment. We also addressed the functions of metabolic regulators within non-myocytes in modulating myocardial microenvironment. Finally, we pointed out some interesting and important questions that are needed to be addressed by further studies.

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Section: The Regulation Of Metabolism Dysfunction On Cardiomyocyte Sementioning

confidence: 99%

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments

2020

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“…Cardiomyocytes were isolated from the heart ventricles of 1-to 3-day neonatal SD rats as described previously (Tang et al, 2016). Neonatal rat cardiomyocytes (NRCMs) were then cultured in DMEM medium supplied with 10% fetal bovine serum (FBS, Gibco), 1% antibiotic-antimycotic (ThermoFisher) for 48 h. The NRCMs were cultured in DMEM with 1% fetal bovine serum for 24 h and then the hypertrophy of NRCMs was induced by angiotensin II (1 µM) treatment for 48 h as reffed from previous publications (Luo et al, 2017;Tang et al, 2017).…”

Section: Isolation and Treatment Of Cardiomyocytementioning

confidence: 99%

The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

Zhao

et al. 2020

Front. Physiol.

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The roles of the histone demethylase JMJD1C in cardiac hypertrophy remain unknown. JMJD1C was overexpressed in hypertrophic hearts of humans and mice, whereas the histone methylation was reduced. Jmjd1c knockdown repressed the angiotensin II (Ang II)-mediated increase in cardiomyocyte size and overexpression of hypertrophic genes in cardiomyocytes. By contrast, JMJD1C overexpression promoted the hypertrophic response of cardiomyocytes. Our further molecular mechanism study revealed that JMJD1C regulated AMP-dependent kinase (AMPK) in cardiomyocytes. JMJD1C did not influence LKB1 but repressed Camkk2 expression in cardiomyocytes. Inhibition of CAMKK2 with STO609 blocked the effects of JMJD1C on AMPK. AMPK knockdown blocked the inhibitory functions of JMJD1C knockdown on Ang II-induced hypertrophic response, whereas metformin reduced the functions of JMJD1C and repressed the hypertrophic response in cardiomyocytes.

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“…To induce in vitro cardiomyocyte hypertrophy, neonatal rat cardiomyocytes from 1-to 3-day-old Sprague-Dawley rats were isolated and used using a previously described protocol [23,24]. The rat cardiomyocytes were cultured in DMEM (HyClone) containing 10% fetal bovine serum (FBS, Thermo Fisher), penicillin/streptomycin (1000 U/ml each; Gibco).…”

Section: Isolation and Culture Of Neonatal Rat Cardiomyocytesmentioning

confidence: 99%

Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling

et al. 2020

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Carboxypeptidase A4 (CPA4) is a member of the metallocarboxypeptidase family. Current studies have identified the roles of CPA4 in cancer biology and insulin sensitivity. However, the roles of CPA4 in other diseases are not known. In the present study, we investigated the roles of CPA4 in cardiac hypertrophy. The expression of CPA4 was significantly increased in the hypertrophic heart tissues of human patients and isoproterenol (ISO)-induced hypertrophic heart tissues of mice. We next knocked down Cpa4 with shRNA or overexpressed Cpa4 using adenovirus in neonatal rat cardiomyocytes and induced cardiomyocyte hypertrophy with ISO. We observed that Cpa4 overexpression promoted whereas Cpa4 knockdown reduced ISO-induced growth of cardiomyocyte size and overexpression of hypertrophy marker genes, such as myosin heavy chain β (β-Mhc), atrial natriuretic peptide (Anp), and brain natriuretic peptide (Bnp). Our further mechanism study revealed that the mammalian target of rapamycin (mTOR) signaling was activated by Cpa4 in cardiomyocytes, which depended on the phosphoinositide 3-kinase (PI3K)-AKT signaling. Besides, we showed that the PI3K-AKT-mTOR signaling was critically involved in the roles of Cpa4 during cardiomyocyte hypertrophy. Collectively, these results demonstrated that CPA4 is a regulator of cardiac hypertrophy by activating the PI3K-AKT-mTOR signaling, and CPA4 may serve as a promising target for the treatment of hypertrophic cardiac diseases.

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SIRT1 deacetylates the cardiac transcription factor Nkx2.5 and inhibits its transcriptional activity

Cited by 29 publications

References 32 publications

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments

The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling

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