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1.
Braz. j. med. biol. res ; 54(2): e10107, 2021. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1142578

ABSTRACT

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug's sustained antidepressant-like effects.


Subject(s)
Animals , Male , Rabbits , Brain/drug effects , Brain/enzymology , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/pharmacology , Antidepressive Agents/pharmacology , Astrocytes , Glycogen Synthase Kinase 3 , Disease Models, Animal , Glial Fibrillary Acidic Protein , Histone Deacetylases
2.
Frontiers of Medicine ; (4): 79-90, 2021.
Article in English | WPRIM | ID: wpr-880969

ABSTRACT

Natural killer (NK) cells, a type of cytotoxic lymphocytes, can infiltrate into ischemic brain and exacerbate neuronal cell death. Astragaloside IV (ASIV) is the major bioactive ingredient of Astragalus membranaceus, a Chinese herbal medicine, and possesses potent immunomodulatory and neuroprotective properties. This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells. ASIV reduced brain infarction and alleviated functional deficits in MCAO rats, and these beneficial effects persisted for at least 7 days. Abundant NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia, and this infiltration was suppressed by ASIV. Strikingly, ASIV reversed NK cell deficiency in the spleen and blood after brain ischemia. ASIV inhibited astrocyte-derived CCL2 upregulation and reduced CCR2


Subject(s)
Animals , Brain , Histone Deacetylases , Killer Cells, Natural , Rats , Saponins/pharmacology , Triterpenes/pharmacology
3.
Frontiers of Medicine ; (4): 91-100, 2021.
Article in English | WPRIM | ID: wpr-880951

ABSTRACT

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Cell Proliferation , Heart Defects, Congenital/genetics , Histone Deacetylases , Humans , RNA, Long Noncoding/genetics , Transcription Factors
4.
Chinese Journal of Biotechnology ; (12): 2645-2657, 2021.
Article in Chinese | WPRIM | ID: wpr-887830

ABSTRACT

Lysine acetylation is one of the major post-translational modifications and plays critical roles in regulating gene expression and protein function. Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from the lysines of both histone and non-histone proteins. The RPD3 family is the most widely studied HDACs. This article summarizes the regulatory mechanisms of Arabidopsis RPD3 family in several growth and development processes, which provide a reference for studying the mechanisms of RPD3 family members in regulating plant development. Moreover, this review may provide ideas and clues for exploring the functions of other members of HDACs family.


Subject(s)
Arabidopsis/metabolism , Histone Deacetylases/metabolism , Histones , Plant Development/genetics
5.
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
6.
Chinese Medical Journal ; (24): 963-970, 2021.
Article in English | WPRIM | ID: wpr-878129

ABSTRACT

BACKGROUND@#Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway.@*METHODS@#Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting.@*RESULTS@#IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells.@*CONCLUSION@#HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.


Subject(s)
Cell Line, Tumor , Cells, Cultured , Chondrocytes/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Histone Deacetylases/genetics , Humans , Interleukin-1beta/pharmacology , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3 , Repressor Proteins , Wnt Signaling Pathway , Wnt3A Protein/genetics , beta Catenin/metabolism
7.
Article in Chinese | WPRIM | ID: wpr-879849

ABSTRACT

OBJECTIVE@#To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development.@*METHODS@#The mice with Synapsin1-Cre recombinase were bred with @*RESULTS@#The mice with @*CONCLUSIONS@#Deletion of


Subject(s)
Animals , Blotting, Western , Histone Deacetylase 1/genetics , Histone Deacetylase 2 , Histone Deacetylases/genetics , Immunohistochemistry , Mice , Neurons/metabolism , Signal Transduction
8.
Article in Chinese | WPRIM | ID: wpr-826722

ABSTRACT

OBJECTIVE@#To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism.@*METHODS@#A total of 35 SD rats were randomized into a sham BCP group (=6), a BCP group (=7), a MT group (=7), a BNA+EA group (=8) and a shame BNA group (=7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot.@*RESULTS@#Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group (0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (<0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group (<0.05, <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (<0.01, <0.05), while the level of MOR was increased (<0.01).@*CONCLUSION@#Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.


Subject(s)
Acupuncture Points , Animals , Bone Neoplasms , Cancer Pain , Therapeutics , Drug Tolerance , Electroacupuncture , Ganglia, Spinal , Metabolism , Histone Deacetylases , Metabolism , Morphine , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu , Metabolism
9.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(6): 485-493, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055347

ABSTRACT

Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.


Subject(s)
Humans , Male , Adult , Young Adult , Crack Cocaine , DNA Methylation , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/blood , Genome-Wide Association Study/methods , Case-Control Studies , Linear Models , Histone-Lysine N-Methyltransferase/genetics , Statistics, Nonparametric , Mitogen-Activated Protein Kinase 1/genetics , MAP Kinase Kinase 1/genetics , Mitogen-Activated Protein Kinase 3/genetics , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Histocompatibility Antigens/genetics , Histone Deacetylases/genetics
10.
Mem. Inst. Oswaldo Cruz ; 114: e190366, 2019. tab, graf
Article in English | LILACS | ID: biblio-1101272

ABSTRACT

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.


Subject(s)
Animals , Female , Pregnancy , Spleen/chemistry , Schistosomiasis mansoni/metabolism , Breast Feeding , Histone Deacetylases/metabolism , Animals, Suckling/parasitology , Pregnancy Complications, Parasitic , Disease Models, Animal , Immunity, Maternally-Acquired , Animals, Suckling/metabolism
11.
Braz. j. med. biol. res ; 52(8): e8341, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011606

ABSTRACT

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.


Subject(s)
Humans , Male , Female , Middle Aged , Repressor Proteins/metabolism , Stomach Neoplasms/pathology , Carcinoma/pathology , MicroRNAs/metabolism , Histone Deacetylases/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , RNA, Messenger/metabolism , Carcinoma/genetics , Carcinoma/metabolism , Down-Regulation , Gene Expression Regulation, Neoplastic , Apoptosis , Disease Progression , Cell Proliferation/genetics , Carcinogenesis/genetics , Neoplasm Staging
12.
Biol. Res ; 52: 20, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011422

ABSTRACT

BACKGROUND: Histone acetylation is an important epigenetic modification that regulates gene activity in response to stress. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The imperative roles of HDACs in gene transcription, transcriptional regulation, growth and responses to stressful environment have been widely investigated in Arabidopsis. However, data regarding HDACs in kenaf crop has not been disclosed yet. RESULTS: In this study, six HDACs genes (HcHDA2, HcHDA6, HcHDA8, HcHDA9, HcHDA19, and HcSRT2) were isolated and characterized. Phylogenetic tree revealed that these HcHDACs shared high degree of sequence homology with those of Gossypium arboreum. Subcellular localization analysis showed that GFP-tagged HcHDA2 and HcHDA8 were predominantly localized in the nucleus, HcHDA6 and HcHDA19 in nucleus and cytosol. The HcHDA9 was found in both nucleus and plasma membranes. Real-time quantitative PCR showed that the six HcHDACs genes were expressed with distinct expression patterns across plant tissues. Furthermore, we determined differential accumulation of HcHDACs transcripts under salt and drought treatments, indicating that these enzymes may participate in the biological process under stress in kenaf. Finally, we showed that the levels of histone H3 and H4 acetylation were modulated by salt and drought stress in kenaf. CONCLUSIONS: We have isolated and characterized six HDACs genes from kenaf. These data showed that HDACs are imperative players for growth and development as well abiotic stress responses in kenaf.


Subject(s)
Stress, Physiological/physiology , Hibiscus/enzymology , Histone Acetyltransferases/physiology , Droughts , Histone Deacetylases/physiology , Transcriptional Activation/physiology , Cloning, Molecular , Hibiscus/growth & development , Hibiscus/physiology , Real-Time Polymerase Chain Reaction
13.
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
14.
Article in Chinese | WPRIM | ID: wpr-781262

ABSTRACT

OBJECTIVE@#To explore the analgesic mechanism of intrathecal trichostatin A (TSA) injection in a rat model of neuropathic pain induced by chronic constrictive injury (CCI).@*METHODS@#Male SD rats were randomized into sham operation+ DMSO group (group S), CCI +DMSO group (group C), CCI +10 μg TSA group (group T), and in the latter two groups, rat models of neuropathic pain were established induced by CCI. The rats were given intrathecal injections of 10 μL 5% DMSO or 10 μg TSA (in 5% DMSO) once a day on days 7 to 9 after CCI or sham operation. The rats were euthanized after behavioral tests on day 10, and the lumbar segment of the spinal cord was sampled to determine the expression of histone deacetylase 4 (HDAC4) protein and mRNA and detect the differentially expressed miRNAs using a miRNA chip. MiR-190b-5p and miR-142-3p were selected for validation of the results using RT-qPCR.@*RESULTS@#Compared with those in group S, the rats in group C showed significantly decreased paw withdrawal mechanical threshold (PWMT) from day 3 to day 10 after CCI ( < 0.05); intrathecal injection of TSA significantly reversed the reduction of PWMT following CCI ( < 0.05). Positive HDAC4 expression was detected mainly in the cytoplasm of the neurons in the gray matter of the spinal cord, and was obviously up-regulated after CCI ( < 0.05). Intrathecal injection of TSA significantly suppressed CCI-induced up-regulation of HDAC4 at 10 days after the operation ( < 0.05). Compared with the miRNA profile in group S, miRNA profiling identified 83 differentially expressed miRNAs in group C (fold change ≥2 or ≤0.5, < 0.05); TSA treatment reversed the expressions of 58 of the differentially expressed miRNAs following CCI, including 41 miRNAs that were decreased after CCI but up-regulated following TSA treatment. The results of real-time PCR validated the changes in the expressions of miR-190b-5p and miR-142-3p.@*CONCLUSIONS@#TSA suppresses CCI-induced up-regulation of HDAC4 and reverses differential expressions of miRNAs in the spinal cord of rats, which may contribute to the analgesic effect of TSA on neuropathic pain.


Subject(s)
Animals , Histone Deacetylases , Hydroxamic Acids , Male , MicroRNAs , Rats , Rats, Sprague-Dawley , Spinal Cord , Up-Regulation
15.
Article in English | WPRIM | ID: wpr-763335

ABSTRACT

OBJECTIVES: To investigate glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) gene expression and protein levels in peripheral blood mononuclear cells (PBMCs) of patients with severe or profound sudden sensorineural hearing loss (SSNHL) and to explore the roles of GRs and HDAC2 in glucocorticoid (GC) insensitivity. METHODS: Fifty-five severe or profound SSNHL patients were enrolled in the study. According to hearing improvement after GC treatment, patients were assigned into two groups: GC-sensitive and GC-resistant. A normal reference group included 20 healthy volunteers without hearing loss. Quantitative real-time polymerase chain reaction and Western blot analyses were used to detect the relative expression of GRα, GRβ, and HDAC2 in PBMCs at the mRNA and protein levels. RESULTS: The protein levels of GRs and HDAC2 in PBMCs of SSNHL patients were lower than the normal reference values before GC treatment. Compared with the GC-resistant group, both the mRNA and protein levels of GRα and HDAC2 were significantly increased in the GC-sensitive group after GC treatment. CONCLUSION: A lack of GRα and HDAC2 induction following steroid treatment in GC-resistant SSNHL patients may play a fundamental mechanistic role in GC insensitivity. Response of GRα and HDAC2 to steroid treatment may, thus, predict the prognosis of hearing improvement in SSNHL patients.


Subject(s)
Blotting, Western , Gene Expression , Healthy Volunteers , Hearing , Hearing Loss , Hearing Loss, Sensorineural , Histone Deacetylase 2 , Histone Deacetylases , Histones , Humans , Prognosis , Real-Time Polymerase Chain Reaction , Receptors, Glucocorticoid , Reference Values , RNA, Messenger
16.
Article in English | WPRIM | ID: wpr-764064

ABSTRACT

BACKGROUND AND OBJECTIVES: Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells. METHODS AND RESULTS: Treatment with the SIRT1 inhibitors, nicotinamide and splitomicin, during the hematopoietic differentiation of ES cells enhanced the production of hematopoietic progenitors and slightly up-regulated erythroid and myeloid specific gene expression. Furthermore, treatment with splitomicin increased the percentage of erythroid and myeloid lineage cells. CONCLUSIONS: Application of the SIRT1 inhibitor splitomicin during ES cell differentiation to hematopoietic cells enhanced the yield of specific hematopoietic lineage cells from ES cells. This result suggests that SIRT1 is involved in the regulation of hematopoietic differentiation of specific lineages and that the modulation of the SIRT1 activity can be a strategy to enhance the efficiency of hematopoietic differentiation.


Subject(s)
Animals , Cell Differentiation , Cell Survival , Chromatin Assembly and Disassembly , Gene Expression , Gene Silencing , Histone Deacetylases , Metabolism , Mice , Mouse Embryonic Stem Cells , Niacinamide
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 Chinese | WPRIM | ID: wpr-776821

ABSTRACT

OBJECTIVE@#To explore the genetic cause of a neonate with congenital dysplasia, growth retardation through clinical evaluation, laboratory tests and next generation sequencing (NGS).@*METHODS@#Peripheral blood samples were obtained from the child and his parents. Whole genomic DNA was extracted and subjected to NGS. Suspected mutation was predicted by bioinformatic tools and validated by Sanger sequencing.@*RESULTS@#The child was found to carry a c.556G>A (p.E186K) mutation of the HDAC8 gene on the X chromosome, which was predicted to be pathogenic by Bioinformatic analysis.@*CONCLUSION@#The patient was diagnosed as Cornelia de Lange syndrome 5 caused by the c.556G>A mutation of the HDAC8 gene.


Subject(s)
De Lange Syndrome , Genetics , Genetic Testing , High-Throughput Nucleotide Sequencing , Histone Deacetylases , Genetics , Humans , Infant, Newborn , Male , Mutation , Repressor Proteins , Genetics
19.
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
20.
Article in Chinese | WPRIM | ID: wpr-773537

ABSTRACT

OBJECTIVE@#Histone deacetylase 11 (HDAC11) is a class Ⅳ member of histone deacetylase family, and its role in regulating cancer cell invasion and metastasis remains unclear. We aimed to investigate the role of HDAC11 in regulating the biological behaviors of basal-like breast cancer (BLBC) cells.@*METHODS@#We analyzed the expression of HDAC11 based on Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). The effects of HDAC11 on the cell invasion and metastasis were examined using Transwell assay and in a mouse model. The interaction between HDAC11 and Twist was detected with immunoprecipitation. We identified 2 as a target gene of Twist using promoter luciferase assay and chromatin immunoprecipitation assay.@*RESULTS@#HDAC11 was lowly expressed in BLBC cells. HDAC11 overexpression suppressed BLBC cell invasion and their metastasis in nude mice. Mechanistically, HDAC11 directly interacted with Twist protein, antagonized its pro-invasive function and repressed Twist-induced 2 gene transcription.@*CONCLUSIONS@#Our data suggest that HDAC11 acts as a negative modulator of invasion and metastasis of BLBC cells.


Subject(s)
Animals , Breast Neoplasms , Histone Deacetylases , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , Promoter Regions, Genetic , Twist-Related Protein 1
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