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1.
Article in Chinese | WPRIM | ID: wpr-921528

ABSTRACT

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.


Subject(s)
Acetylation , Aging , Animals , Liver , Lysine/metabolism , Male , Mice , Mice, Inbred C57BL , Proteome/metabolism
2.
Acta Physiologica Sinica ; (6): 527-534, 2021.
Article in Chinese | WPRIM | ID: wpr-887688

ABSTRACT

Oogenesis is the basic reproductive process of female mammals and is essential for fertilization and embryo development. Recent studies have shown that epigenetic modifications play an important role in the regulation of mammalian reproductive processes (such as oogenesis, spermatogenesis, preimplantation embryo development and sex differentiation). Taking histone acetylation as an instance, the dynamic changes of histone acetyltransferases (HATs) and deacetylases (HDACs) are involved in the regulation of gene activation and inactivation when numerous key physiological events occur during reproduction. Thereinto, HDAC1 and HDAC2, which are highly homologous in terms of both structure and function, play a pivotal role in murine oogenesis. HDAC1 and 2 jointly regulate the global transcription and the incidence of apoptosis of growing oocytes and affect its subsequent growth and development, which reflects their compensatory function. In addition, HDAC1 and 2 also play a specific part in oogenesis respectively. It has shown that HDAC2 is more critical than HDAC1 for oocyte development, which regulates de novo DNA methylation and chromosome segregation. Reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. Deficiency of HDAC1 causes the decreased proliferation of embryonic stem cells and the smaller embryoid bodies with irregular shape. In this review, we summarized the role and the current research progress of HDAC1/2 in murine oogenesis, to provide a reference for further understanding the relationship between epigenetic modifications and reproductive regulation.


Subject(s)
Acetylation , Animals , Embryonic Development , Female , Histone Deacetylase 1/metabolism , Histone Deacetylase 2/metabolism , Histone Deacetylases/metabolism , Male , Mice , Oocytes , Oogenesis
3.
Braz. j. med. biol. res ; 53(10): e9861, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132476

ABSTRACT

Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.


Subject(s)
Animals , Female , Pregnancy , Rats , Cognitive Dysfunction , Acetylation , Histones , Maze Learning , Brain-Derived Neurotrophic Factor , Sevoflurane , Hippocampus
4.
Article in Chinese | WPRIM | ID: wpr-878682

ABSTRACT

Proteins exert their roles in life activities via post-translational modifications(PTMs),which include phosphorylation,acetylation,ubiquitination,glycosylation,and methylation.These modifications can change the functions of proteins and play key roles in a variety of diseases.Endometriosis is a common disease in women of childbearing age,although its molecular mechanisms remain unclear.Recent studies have shown that PTMs may be involved in the pathogenesis of endometriosis.Here we review the roles of PTMs in the occurrence and development of endometriosis and the potential medical treatments.


Subject(s)
Acetylation , Endometriosis/pathology , Female , Glycosylation , Humans , Phosphorylation , Protein Processing, Post-Translational , Ubiquitination
5.
Article in English | WPRIM | ID: wpr-880485

ABSTRACT

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.


Subject(s)
Acetylation , Lysine/metabolism , Oryza/metabolism , Plant Proteins/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Proteome/metabolism , Ubiquitin/metabolism , Ubiquitination
6.
Braz. arch. biol. technol ; 63: e20180292, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132184

ABSTRACT

Abstract Acetylated cassava starch with low and medium degrees of substitution (DS) were synthesized. Also, the effect of DS on swelling power, solubility, morphological properties, gelatinization temperature, paste clarity and moisture sorption were studied. Swelling power and solubility in water between 50ºC and 90°C were determined. Acetylated cassava starches with low DS showed an increased in both parameters, while at higher DS values a reduction of them was observed. Maximum swelling power values were measured in acetylated starch with DS of 0.2 and maximum solubility was registered at DS of 0.72. Equilibrium moisture content values from sorption isotherms presented a good fit using the GAB model (R2>0.96). SEM micrographs showed that as acetyl groups are incorporated the granules suffer surface changes and eventually lose their structure at DS of 1.5. Clarity of acetylated starch pastes with low DS was lighter than native starch paste. In addition, the increase in DS produced a reduction in gelatinization temperature.


Subject(s)
Acetylation , Solubility , Substantia Gelatinosa , Temperature , Starch and Fecula , Microscopy, Electron, Scanning
7.
Univ. med ; 60(2): 1-25, 2019. ilus, tab
Article in Spanish | LILACS, COLNAL | ID: biblio-994578

ABSTRACT

Para acortar la brecha entre lo molecular y la clínica, el personal de atención médica debe tener un conocimiento básico de los mecanismos moleculares que gobiernan la identidad celular, mediante la activación selectiva de genes. La expresión diferencial de genes permite a las células sintetizar las proteínas requeridas para cumplir con sus funciones biológicas, y ello posibilita a las células responder a estímulos internos y externos. Para esto se debe tener primero acceso a los genes que codifican las proteínas, determinando el fenotipo celular. Modificaciones en la estructura de la cromatina permiten a la maquinaria transcripcional tener acceso a secuencias de ADN. El ADN es transcripto en ARNm, que sufre diversas modificaciones antes de salir del núcleo para ser traducido en una proteína en el citoplasma. Cualquier desregulación en alguno de los procesos asociados se presenta como una patología. A inicios del siglo XXI se reportó la secuenciación del genoma humano, y sorprendentemente uno de los principales hallazgos fue que solo un 2% de la secuencia codifica para proteínas, lo cual dejó un interrogante sobre cómo funcionan y se regulan los procesos genéticos que llevan a la identidad celular. Desde entonces las investigaciones han permitido utilizar los principios que rigen estos procesos para ampliar el conocimiento de los mecanismos asociados a enfermedades. Gracias a estos avances, se ha buscado determinar aplicaciones clínicas dirigidas a los procesos involucrados en la expresión génica diferencial, lograr una mejor comprensión sobre los procesos patológicos de la enfermedad y desarrollar herramientas diagnósticas.


To narrow the gap between the bench and the clinic, healthcare personnel should have a basic understanding of molecular mechanisms ruling cell identity, since it establishes the key differences between health and disease states. Differential gene expression allows for protein synthesis required for the cell's biological function. In this process genes are selected from the entire genome to meet the cell's biological functioning and respond to internal and external stimuli. To this end, first the chromatin must be remodeled for the transcriptional machinery to gain access to DNA sequences coding for particular genes. DNA can then be transcribed into mRNA, followed by different processes leading to mature mRNA leaving the nucleus for protein synthesis in the cytoplasm. Any dysregulation in these processes results in disease. In the beginning of this millennium the human genome project sequenced the whole genome. Surprisingly, one of the main findings was only 2% of the genome represented protein coding sequences, which raised the question about the remainder of the genome and cell identity. Based on principles derived from the human genome project many investigations have shed light on mechanisms associated with disease. Thanks to advancements in differential gene expression, researchers are seeking for a better understanding in pathological processes associated with disease and the development of diagnostic tools.


Subject(s)
Humans , Epigenomics , Acetylation , Methylation
8.
Article in English | WPRIM | ID: wpr-765654

ABSTRACT

Diabetes mellitus increases the risk for the development of heart failure even in the absence of coronary artery disease and hypertension, a cardiac entity termed diabetic cardiomyopathy (DC). Clinically, DC is increasingly recognized and typically characterized by concentric cardiac hypertrophy and diastolic dysfunction, ultimately resulting in heart failure with preserved ejection fraction (HFpEF) and potentially even heart failure with reduced ejection fraction (HFrEF). Numerous molecular mechanisms have been proposed to underlie the alterations in myocardial structure and function in DC, many of which show similar alterations in the failing heart. Well investigated and established mechanisms of DC include increased myocardial fibrosis, enhanced apoptosis, oxidative stress, impaired intracellular calcium handling, substrate metabolic alterations, and inflammation, among others. In addition, a number of novel mechanisms that receive increasing attention have been identified in recent years, including autophagy, dysregulation of microRNAs, epigenetic mechanisms, and alterations in mitochondrial protein acetylation, dynamics and quality control. This review aims to provide an overview and update of established underlying mechanisms of DC, as well as a discussion of recently identified and emerging mechanisms that may also contribute to the structural and functional alterations in DC.


Subject(s)
Acetylation , Apoptosis , Autophagy , Calcium , Cardiomegaly , Coronary Artery Disease , Diabetes Mellitus , Diabetic Cardiomyopathies , Epigenomics , Fibrosis , Heart , Heart Failure , Hypertension , Inflammation , MicroRNAs , Mitochondrial Proteins , Oxidative Stress , Quality Control
9.
Article in English | WPRIM | ID: wpr-763040

ABSTRACT

HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.


Subject(s)
Acetylation , Adenosine Triphosphate , Binding Sites , Drug Therapy , Hand , Heat-Shock Proteins , Histone Deacetylase Inhibitors , Hot Temperature , Indicators and Reagents , Molecular Chaperones , Rifabutin
10.
Article in English | WPRIM | ID: wpr-765052

ABSTRACT

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.


Subject(s)
Acetylation , Alzheimer Disease , Brain , Central Nervous System , Computational Biology , Diptera , Down-Regulation , Drosophila melanogaster , Drosophila , Heterochromatin , Histones , Humans , Locomotion , Methylation , Neurodegenerative Diseases , Neurofibrillary Tangles , Pathology , Phenotype , RNA, Messenger , tau Proteins , Tauopathies , Transcriptome
11.
Article in English | WPRIM | ID: wpr-772940

ABSTRACT

Enhancers activate transcription in a distance-, orientation-, and position-independent manner, which makes them difficult to be identified. Self-transcribing active regulatory region sequencing (STARR-seq) measures the enhancer activity of millions of DNA fragments in parallel. Here we used STARR-seq to generate a quantitative global map of rice enhancers. Most enhancers were mapped within genes, especially at the 5' untranslated regions (5'UTR) and in coding sequences. Enhancers were also frequently mapped proximal to silent and lowly-expressed genes in transposable element (TE)-rich regions. Analysis of the epigenetic features of enhancers at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and lack the enhancer mark of histone modification H3K4me1. Clustering analysis of enhancers according to their epigenetic marks revealed that about 40% of identified enhancers carried one or more epigenetic marks. Repressive H3K27me3 was frequently enriched with positive marks, H3K4me3 and/or H3K27ac, which together label enhancers. Intergenic enhancers were also predicted based on the location of DHS regions relative to genes, which overlap poorly with STARR-seq enhancers. In summary, we quantitatively identified enhancers by functional analysis in the genome of rice, an important model plant. This work provides a valuable resource for further mechanistic studies in different biological contexts.


Subject(s)
Acetylation , Base Sequence , Deoxyribonuclease I , Metabolism , Enhancer Elements, Genetic , Epigenesis, Genetic , Genes, Plant , Genomics , Methods , Histone Code , Genetics , Histones , Metabolism , Models, Genetic , Oryza , Genetics , Promoter Regions, Genetic , Genetics , Repetitive Sequences, Nucleic Acid , Genetics , Sequence Analysis, DNA , Transcription, Genetic
12.
Article in Chinese | WPRIM | ID: wpr-772690

ABSTRACT

Epigenetics is defined as a change in gene expression without the alteration of the genetic sequence. Such a change would be inherited by offspring. Histone acetylation is a type of epigenetics. Existing studies proposed that chronic periodontitis is related to epigenetic modification. In this review, we summarised the influence of chronic periodontitis on periodontal ligament stem cells by histone acetylation.


Subject(s)
Acetylation , Cell Differentiation , Cells, Cultured , Histones , Metabolism , Osteogenesis , Periodontal Ligament , Stem Cells , Physiology
13.
Article in English | WPRIM | ID: wpr-772264

ABSTRACT

There are large knowledge gaps regarding how to control stem cells growth and differentiation. The limitations of currently available technologies, such as growth factors and/or gene therapies has led to the search of alternatives. We explore here how a cell's epigenome influences determination of cell type, and potential applications in tissue engineering. A prevalent epigenetic modification is the acetylation of DNA core histone proteins. Acetylation levels heavily influence gene transcription. Histone deacetylase (HDAC) enzymes can remove these acetyl groups, leading to the formation of a condensed and more transcriptionally silenced chromatin. Histone deacetylase inhibitors (HDACis) can inhibit these enzymes, resulting in the increased acetylation of histones, thereby affecting gene expression. There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering, potentially providing novel tools to control stem cell fate. This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone, cardiac, neural tissues), including the history, current status and future perspectives of using HDACis for stem cell research and tissue engineering, with particular attention paid to how different HDAC isoforms may be integral to this field.


Subject(s)
Acetylation , Histone Deacetylase Inhibitors , Pharmacology , Histone Deacetylases , Metabolism , Histones , Metabolism , Humans , Tissue Engineering
14.
Article in English | WPRIM | ID: wpr-760610

ABSTRACT

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.


Subject(s)
Acetylation , Dietary Supplements , Epigenomics , Hep G2 Cells , Histone Acetyltransferases , Histones , Lipid Metabolism , Lipogenesis , Liver , Lysine , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , RNA, Messenger , Sterol Regulatory Element Binding Protein 1
15.
Article in English | WPRIM | ID: wpr-785915

ABSTRACT

BACKGROUND: Beta-carotene (BC) is a carotenoid which exerts anti-cancer effects in several types of cancer, including colorectal cancer. Epigenetic modifications of genes, such as histone deacetylation and DNA hypermethylation, have also been detected in various types of cancer. To understand the molecular mechanism underlying cancer preventive and therapeutic effects of BC, microRNAs (miRNAs), histone acetylation, and global DNA methylation in colon cancer stem cells (CSCs) were investigated.METHODS: HCT116 colon cancer cells positive for expression of CD44 and CD133 were sorted by flow cytometry and used in subsequent experiments. Cell proliferation was examined by the MTT assay and self-renewal capacity was analyzed by the sphere formation assay. The miRNA sequencing array was used to detect miRNAs regulated by BC. Histone acetylation levels were measured by the Western blot analysis. mRNA expression of DNA methyltransferases (DNMTs) was examined by qPCR and global DNA methylation levels were determined by enzyme-linked immunosorbent assay.RESULTS: Treatment of CD44⁺CD133⁺ colon CSCs with BC caused a reduction in both cell proliferation and sphere formation. Analysis of the miRNA sequencing array showed that BC regulated expression of miRNAs associated with histone acetylation. Histone H3 and H4 acetylation levels were elevated by BC treatment. In addition, BC treatment down-regulated DNMT3A mRNA expression and global DNA methylation in colon CSCs.CONCLUSIONS: These results suggest that BC regulates epigenetic modifications for its anti-cancer effects in colon CSCs.


Subject(s)
Acetylation , beta Carotene , Blotting, Western , Cell Proliferation , Colon , Colonic Neoplasms , Colorectal Neoplasms , DNA Methylation , DNA , Enzyme-Linked Immunosorbent Assay , Epigenomics , Flow Cytometry , Histones , Methyltransferases , MicroRNAs , RNA, Messenger , Stem Cells , Therapeutic Uses
16.
Experimental Neurobiology ; : 504-515, 2019.
Article in English | WPRIM | ID: wpr-763777

ABSTRACT

Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD.


Subject(s)
Acetylation , Animals , Cell Survival , Dopaminergic Neurons , Epigenomics , Gene Expression , Histone Deacetylases , Histones , Lewy Bodies , Mice , Mice, Transgenic , Microglia , Models, Genetic , Movement Disorders , Neurodegenerative Diseases , Neurons , Neuroprotection , RNA, Messenger , Substantia Nigra , Tyrosine 3-Monooxygenase , Valproic Acid
17.
Immune Network ; : e9-2019.
Article in English | WPRIM | ID: wpr-740219

ABSTRACT

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.


Subject(s)
Acetylation , Animals , Butyrates , Communicable Diseases , Diethylpropion , Fatty Acids, Volatile , Histone Deacetylase Inhibitors , Histone Deacetylases , Histones , Humans , Inflammation , Lipoproteins , Lysine , Macrophages , Mice , Nitric Oxide Synthase , Nitric Oxide , Phosphorylation , Staphylococcus aureus , Virulence
18.
Article in English | WPRIM | ID: wpr-691344

ABSTRACT

<p><b>OBJECTIVE</b>To examine the effect of icariin (ICA) on the cognitive impairment induced by traumatic brain injury (TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level.</p><p><b>METHODS</b>The modifified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150 mg/kg) of ICA groups. An additional sham-operated group (vehicle-treated) was employed. The vehicle or ICA was administrated by gavage for 28 consecutive days. The Morris water maze (MWM) test was conducted. Acetylcholine (ACh) content, mRNA and protein levels of choline acetyltransferase (ChAT), and protein levels of acetylated H3 (Ac-H3) and Ac-H4 were detected in the hippocampus.</p><p><b>RESULTS</b>Compared with the sham-operated group, the MWM performance, hippocampal ACh content, mRNA and protein levels of ChAT, and protein levels of Ac-H3 and Ac-H4 were signifificantly decreased in the TBI group (P<0.05). High-dose of ICA signifificantly ameliorated the TBI-induced weak MWM performance, increased hippocampal ACh content, and mRNA and protein levels of ChAT, as well as Ac-H3 protein level compared with the TBI group (P<0.05).</p><p><b>CONCLUSION</b>ICA improved post-TBI cognitive impairment in mice by enhancing hippocampal acetylation, which improved hippocampal cholinergic function and ultimately improved cognition.</p>


Subject(s)
Acetylation , Acetylcholine , Metabolism , Animals , Brain Injuries, Traumatic , Choline O-Acetyltransferase , Genetics , Metabolism , Cognitive Dysfunction , Drug Therapy , Flavonoids , Chemistry , Pharmacology , Therapeutic Uses , Hippocampus , Pathology , Histones , Metabolism , Homeostasis , Male , Maze Learning , Mice , RNA, Messenger , Genetics , Metabolism
19.
Journal of Breast Cancer ; : 112-123, 2018.
Article in English | WPRIM | ID: wpr-714870

ABSTRACT

PURPOSE: The incidence and mortality of breast cancer is increasing worldwide. There is a constant quest to understand the underlying molecular biology of breast cancer so as to plan better treatment options. The purpose of the current study was to characterize the expression of histone deacetylases-3 (HDAC3), a member of class I HDACs, and assess the clinical significance of HDAC3 in breast cancer. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry, and western blot analysis were used to examine messenger RNA and protein expression levels. The relationships between HDAC3 expression and clinicopathological variables were analyzed. MTT assays were used to detect cell proliferation. Glucose-uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were employed to detect aerobic glycolysis. Chromatin immunoprecipitation was used to detect microRNA-31 (miR-31) promoter binding. RESULTS: Our data revealed that HDAC3 was upregulated in breast cancer tissue compared with matched para-carcinoma tissues, and high levels of HDAC3 were positively correlated with advanced TNM stage and N stage of cancer. Furthermore, overexpression of HDAC3 promoted breast cancer cell-proliferation and aerobic glycolysis. The functional involvement of HDAC3 was related in part to the repression of miR-31 transcription via decreased histone H3 acetylation at lysine K9 levels of the miR-31 promoter. Survival analysis revealed that the level of HDAC3 was an independent prognostic factor for breast cancer patients. CONCLUSION: Our findings revealed that HDAC3 served as an oncogene that could promote cell proliferation and aerobic glycolysis and was predictive of a poor prognosis in breast cancer. HDAC3 participated in the cell proliferation of breast cancer, which may prove to be a pivotal epigenetic target against this devastating disease.


Subject(s)
Acetylation , Adenosine Triphosphate , Blotting, Western , Breast Neoplasms , Breast , Cell Proliferation , Chromatin Immunoprecipitation , Epigenomics , Glycolysis , Histone Code , Histones , Humans , Immunohistochemistry , Incidence , L-Lactate Dehydrogenase , Lactic Acid , Lysine , Molecular Biology , Mortality , Oncogenes , Prognosis , Real-Time Polymerase Chain Reaction , Repression, Psychology , RNA, Messenger
20.
Article in Chinese | WPRIM | ID: wpr-776687

ABSTRACT

OBJECTIVE@#To study the interactive regulatory effect of histone acetylation and methylation on cardiomyogenesis, and to provide a theoretical basis for the prevention and treatment of congenital heart disease.@*METHODS@#A total of 24 Kunming mice were randomly divided into embryo day 14.5 (ED 14.5) group, embryo day 16.5 (ED 16.5) group, postnatal day 0.5 (PND 0.5) group, and postnatal day 7 (PND 7) group, with 6 mice in each group, and the heart tissue of fetal and neonatal mice was collected. Colorimetry was used to measure the activities of histone acetylases (HATs) and histone methyltransferases (HMTs) in the myocardium. Western blot was used to measure the expression of H3K9ac and H3K9me3 in the myocardium.@*RESULTS@#Colorimetry showed that the activities of HATs and HMTs were higher before birth and were lower after birth. There was a significant difference in the activity of HATs in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 group (P<0.05), as well as between the PND 7 group and the ED 16.5 group (P<0.05). There was also a significant difference in the activity of HMTs in the myocardium between the PND 7 group and the ED 14.5 and ED 16.5 groups (P<0.05). Western blot showed higher expression of H3K9ac and H3K9me3 before birth and lower expression of H3K9ac and H3K9me3 after birth, and there were significant differences in the expression H3K9ac and H3K9me3 in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 and ED 16.5 groups (P<0.05).@*CONCLUSIONS@#The dynamic expression of HATs, HMTs, H3K9ac, and H3K9me3 is observed during cardiomyogenesis, suggesting that histone H3K9ac acetylation and histone H3K9me3 methylation mediated by HATs and HMTs may play a role in interactive regulation during cardiomyogenesis.


Subject(s)
Acetylation , Animals , Histone Acetyltransferases , Histones , Metabolism , Methylation , Mice , Protein Processing, Post-Translational
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