Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event this process is nuclear acetylation by histone deacetylases and p300, an intrinsic acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for yellow color spice turmeric, possesses HAT inhibitory activity with specificity p300/CREB-binding protein. We found curcumin inhibited hypertrophy-induced DNA-binding abilities GATA4,...

Background: MicroRNAs (miRNAs) regulate various biological processes through inhibiting the translation of RNA transcripts. Although miRNA-1 (miR-1) and miRNA-133 (miR-133) are abundantly expressed in adult heart involved cardiac hypertrophy, roles these miRNAs spontaneous myocardial differentiation unknown. Methods Results: The levels miR-1 miR-133 mouse embryonic stem (ES) cells were increased during by 2-dimensional culture, but reduced forced a histone deacetylase inhibitor, trichostatin...

Background: A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs). Methods and Results: Rats were subjected to a sham operation left coronary artery ligation. One week later, 34 rats moderate sized myocardial infarction (MI) randomly assigned 4 groups:...

A zinc finger protein, GATA4, is one of the hypertrophy-responsive transcription factors and increases its DNA binding transcriptional activities in response to hypertrophic stimuli cardiac myocytes. Activation GATA4 during this process mediated, part, through acetylation by intrinsic histone acetyltransferases such as a coactivator p300. However, p300-targeted acetylated sites myocardial cell hypertrophy have not been identified. By mutational analysis, we showed that 4 lysine residues...

MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in regulation the heart. To examine role miRNAs two isoforms cardiac myosin heavy chain (MHC) gene, α- β-MHC, which regulate contractility, endogenous were downregulated neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosynthesis, MHC levels examined. As a result, Dicer siRNA could downregulate...

A zinc finger protein GATA4 is one of the hypertrophy-responsive transcription factors and forms a complex with an intrinsic histone acetyltransferase, p300. Disruption this results in inhibition cardiomyocyte hypertrophy heart failure vivo. By tandem affinity purification mass spectrometric analyses, we identified cyclin-dependent kinase-9 (Cdk9) as novel GATA4-binding partner. Cdk9 also formed p300 well cyclin T1. We showed that was required for interaction kinase activity Cdk9....

The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, factor-C (VEGF-C) pivotal role lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C elevated sera obese subjects. However, relationships with risk factors atherosclerosis unknown. We determined circulating 423 consecutive subjects receiving any drugs at Health Evaluation...

It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined effect EPA on M1/M2-like phenotypes peripheral blood monocytes obese dyslipidemic patients.Peripheral were prepared from 26 patients...

Mouse and human fibroblasts can be directly reprogrammed to pluripotency by the ectopic expression of four transcription factors (Oct3/4, Sox2, Klf4, c-Myc) yield induced pluripotent stem (iPS) cells. iPS cells generated even without c-Myc. The present study examined patterns differentiation mouse into cardiomyocytes in three different cell lines or factors. During induction on feeder-free gelatinized dishes, genes involved cardiogenesis were expressed as embryonic myogenic contraction...

Abstract Myoblasts play a central role during skeletal muscle formation and growth. Precise understanding of myoblast properties is thus indispensable for meat production. Herein, we report the cellular characteristics gene expression profiles primary-cultured myoblasts layer broiler chickens. Broiler actively proliferated promptly differentiated into myotubes compared to myoblasts, which corresponds well with phenotype broilers. Transcriptomes differentiation were quantified by RNA...

Wooden breast syndrome (WB) constitutes an emerging myopathy in the pectoralis major muscle (PM) of broiler chickens, characterized by myofiber hypertrophy and degeneration along with severe fibrosis. WB pathogenesis has been considered to involve hypoxia induced rapid growth PM. In this study, we focused on mitochondrial morphology dynamics myofibers as these organelles are sensitive damage hypoxia, examined effects pathogenesis. Specifically, PMs a flock 35 broilers at 55 days age were...

Herein we report that the 18-base telomeric oligodeoxynucleotides (ODNs) designed from Lactobacillus rhamnosus GG genome promote differentiation of skeletal muscle myoblasts which are myogenic precursor cells. We termed these myogenetic ODNs (myoDNs). The activity one myoDNs, iSN04, was independent Toll-like receptors, but dependent on its conformational state. Molecular simulation and iSN04 mutants revealed stacking 13–15th guanines as a core structure for iSN04. alkaloid berberine bound to...

Skeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased mass and strength, serious risk factor that may result mortality. Deteriorated differentiation precursor cells, called myoblasts, DM considered to be one the causes wasting. We recently developed myogenetic oligodeoxynucleotides (myoDNs), which are 18-base single-strand DNAs promote myoblast by targeting nucleolin. Herein, we report applicability myoDN, iSN04, myoblasts isolated from type 1 2 DM....

Abstract A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5’-AGA TTA GGG TGA TGA-3’), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which expected to be nucleic acid drug for the prevention of disease-associated muscle wasting. To improve efficacy synthesis cost myoDN, shortening sequence while maintaining its structure-based function major challenge. Here, we report novel 12-base non-telomeric iMyo01 (5’-TTG GGT...

A myogenetic oligodeoxynucleotide (myoDN), iSN04 (5′-AGA TTA GGG TGA TGA-3′), is a single-stranded 18-base telomeric DNA that serves as an anti-nucleolin aptamer and induces myogenic differentiation, which expected to be nucleic acid drug for the prevention of disease-associated muscle wasting. To improve efficacy synthesis cost myoDN, shortening sequence while maintaining its structure-based function major challenge. Here, we report novel 12-base non-telomeric iMyo01 (5′-TTG GGT GAA-3′),...

De-differentiation and subsequent increased proliferation inflammation of vascular smooth muscle cells (VSMCs) is one the mechanisms atherogenesis. Maintaining VSMCs in a contractile differentiated state therefore promising therapeutic strategy for atherosclerosis. We have reported 18-base myogenetic oligodeoxynucleotide, iSN04, which serves as an anti-nucleolin aptamer promotes skeletal myocardial differentiation. The present study investigated effect iSN04 on because nucleolin has been to...

Smoking induces vascular inflammation and increases the risk of cardiovascular events. Lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that induced by oxidative stress associated with atherosclerotic plaque formation destabilization. LOX-1 interacts C-reactive protein (CRP) plays an important role in inflammatory diseases. We therefore hypothesized may be involved onset smoking-induced inflammation.We measured soluble (sLOX-1) levels sera obtained from...

Embryonal rhabdomyosarcoma (ERMS) is the muscle-derived tumor retaining myogenic ability. iSN04 and AS1411, which are myogenetic oligodeoxynucleotides (myoDNs) serving as anti-nucleolin aptamers, have been reported to inhibit proliferation induce differentiation of myoblasts. The present study investigated effects AS1411 in vitro on growth multiple patient-derived ERMS cell lines, ERMS1, KYM1, RD. RT-PCR immunostaining revealed that nucleolin was abundantly expressed localized nucleoplasm...

An 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, acts as an anti-nucleolin aptamer and induces myogenic differentiation of skeletal muscle myoblasts. This study investigated the effect iSN04 on murine embryonic stem cells (ESCs) induced pluripotent (iPSCs). In undifferentiated state, inhibited proliferation ESCs iPSCs but did not affect expression markers. differentiating condition, treatment ESCs/iPSCs from day 5 onward dramatically into Nkx2-5+ beating cardiomyocytes with...

Dysfunction of bone-forming cells, osteoblasts, is one the causes osteoporosis. Accumulating evidence has indicated that oligodeoxynucleotides (ODNs) designed from genome sequences have potential to regulate osteogenic cell fate. Such osteogenetic ODNs (osteoDNs) targeting and activating osteoblasts can be candidates nucleic acid drugs for In this study, ODN library derived Lacticaseibacillus rhamnosus GG was screened determine its effect on murine osteoblast line MC3T3-E1. An 18-base ODN,...