Inhibition of Histone Methyltransferase, Histone Deacetylase, and <i>β</i>-Catenin Synergistically Enhance the Cardiac Potential of Bone Marrow Cells

Yang, Jinpu; Kaur, Keerat; Edwards, John G.; Eisenberg, Carol A.; Eisenberg, Leonard M.

doi:10.1155/2017/3464953

Cited by 4 publications

(4 citation statements)

References 66 publications

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“…The result with fruit flies contrasts with the ability of butyrate or trichostatin A treatment to increase both histone H3 and H4 acetylation in mammalian cells [ 366 , 367 ]. In mammalian cells trichostatin A was shown to increase the acetylation of many acetylation marks including histone H3K9, H3K27 [ 368 ], H3K56 [ 369 ], H4K12 [ 370 ], H4K5 [ 371 ], H4K8, H4K16 [ 372 ] and H4K20 [ 373 ], although results are cell-type specific.…”

Section: Fruit Fly Changes In Histone Lysine Acetylation Marks With Aging and Anti-aging Dietary Restrictionmentioning

confidence: 99%

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Bradshaw

2021

Antioxidants

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Acetyl-CoA is a metabolite at the crossroads of central metabolism and the substrate of histone acetyltransferases regulating gene expression. In many tissues fasting or lifespan extending calorie restriction (CR) decreases glucose-derived metabolic flux through ATP-citrate lyase (ACLY) to reduce cytoplasmic acetyl-CoA levels to decrease activity of the p300 histone acetyltransferase (HAT) stimulating pro-longevity autophagy. Because of this, compounds that decrease cytoplasmic acetyl-CoA have been described as CR mimetics. But few authors have highlighted the potential longevity promoting roles of nuclear acetyl-CoA. For example, increasing nuclear acetyl-CoA levels increases histone acetylation and administration of class I histone deacetylase (HDAC) inhibitors increases longevity through increased histone acetylation. Therefore, increased nuclear acetyl-CoA likely plays an important role in promoting longevity. Although cytoplasmic acetyl-CoA synthetase 2 (ACSS2) promotes aging by decreasing autophagy in some peripheral tissues, increased glial AMPK activity or neuronal differentiation can stimulate ACSS2 nuclear translocation and chromatin association. ACSS2 nuclear translocation can result in increased activity of CREB binding protein (CBP), p300/CBP-associated factor (PCAF), and other HATs to increase histone acetylation on the promoter of neuroprotective genes including transcription factor EB (TFEB) target genes resulting in increased lysosomal biogenesis and autophagy. Much of what is known regarding acetyl-CoA metabolism and aging has come from pioneering studies with yeast, fruit flies, and nematodes. These studies have identified evolutionary conserved roles for histone acetylation in promoting longevity. Future studies should focus on the role of nuclear acetyl-CoA and histone acetylation in the control of hypothalamic inflammation, an important driver of organismal aging.

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Section: Fruit Fly Changes In Histone Lysine Acetylation Marks With Aging and Anti-aging Dietary Restrictionmentioning

confidence: 99%

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Bradshaw

2021

Antioxidants

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“…Analysis of phenotypic changes occurring within explants was performed by immunofluorescent staining, as previously described [10,[12][13][14]. All antibodies were used at dilutions recommended by the manufacturer.…”

Section: Immunofluorescence Analysismentioning

confidence: 99%

Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro

Eisenberg,

Kaur,

Castillo

et al. 2023

IJTM

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Normal contractile function of the myocardium is essential for optimal cardiovascular health. Evaluating drug effects on cardiomyocyte function at the cellular level is difficult for long-term studies. Present culture systems rely on isolated, cardiomyocyte preparations or cardiomyocytes derived from pluripotent stem cells (PSCs), all of which have limitations. Isolated, endogenous cardiomyocytes do not remain contractile in culture long term. While PSC-derived cardiomyocytes show contractile activity for longer periods of time, their phenotype is more embryonic than adult. Here we report that dexamethasone (DEX) treatment of adult mouse atrial tissue can extend its functionality in culture. Normally, cardiac explants cease their capacity as a contractile tissue within the first month, as the tissue flattens and spreads out on the culture substrate, while the cells dedifferentiate and lose their myocardial phenotype. However, with DEX treatment, cardiac explants maintain their contractile function, 3D morphology, and myocyte phenotype for up to 6 months. Moreover, DEX also preserved the contractile phenotype of isolated rat cardiomyocytes. These data with DEX suggest that simple modifications in culture conditions can greatly improve the long-term utility of in vitro model systems for screening drugs and agents that could be employed to alleviate human cardiac disease.

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“…Each experiment was repeated three times. The relative mRNA expression levels were quantified using the 2 -ΔΔCq method (9,12), and normalized to GAPDH.…”

Section: Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

G9a inhibition promotes the formation of pacemaker-like cells by reducing the enrichment of H3K9me2 in the HCN4 promoter region

Jin

Zhou

et al. 2022

Mol Med Rep

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Biological pacemakers, made of pacemaker-like cells, are promising in the treatment of bradyarrhythmia; however, the inefficiency of stem cell differentiation into pacemaker-like cells has limited their clinical application. Previous studies have reported that histone H3 at lysine 9 (H3K9) methylation is widely involved in the proliferation and differentiation of cardiomyocytes, but the specific role of H3K9 dimethylation (H3K9me2) in the formation of pacemaker cells remains unclear. The present study evaluated the functional role of H3K9me2 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells. Rat BMSCs pretreated with the euchromatic histone lysine methyltransferase 2 (G9a) inhibitor BIX01294 were transfected with a T-box 18 overexpression plasmid to induce BMSCs to form pacemaker-like cells. The induced pacemaker-like cells were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and immunofluorescence to assess the efficiency of differentiation. The enrichment of H3K9me2 in the hyperpolarized-activated cyclic nucleotide-gated cation channel (HCN)4 promoter region was assessed by chromatin immunoprecipitation (ChIP). In addition, BIX01294 was injected into rats, and the protein and mRNA expression levels of HCN4 were assessed using western blotting and RT-qPCR. After interference with G9a using BIX01294, ChIP results demonstrated that H3K9me2 levels in the promoter region of HCN4 were markedly decreased. Immunofluorescence and RT-qPCR demonstrated that the protein expression levels of certain cardio-specific proteins in the treated group were significantly higher compared with those in the untreated group. In vivo experiments demonstrated that interference with G9a could cause pathological hypertrophy. Furthermore, in vitro and in vivo inhibition of G9a could increase the differentiation and proliferation of pacemaker-like cells by decreasing the levels of H3K9me2 in the promoter region of HCN4 gene.

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Inhibition of Histone Methyltransferase, Histone Deacetylase, and β-Catenin Synergistically Enhance the Cardiac Potential of Bone Marrow Cells

Cited by 4 publications

References 66 publications

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro

G9a inhibition promotes the formation of pacemaker-like cells by reducing the enrichment of H3K9me2 in the HCN4 promoter region

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