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1.
Article in English | WPRIM | ID: wpr-929069

ABSTRACT

Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 (Prdm1) and X-box-binding protein 1 (Xbp1), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.


Subject(s)
Animals , Depsipeptides , Endoribonucleases , Hematopoietic Stem Cell Transplantation , Histone Deacetylase Inhibitors/pharmacology , Mice , Protein Serine-Threonine Kinases , Skin Transplantation
2.
Article in Chinese | WPRIM | ID: wpr-878706

ABSTRACT

The self-renewal and differentiation of hematopoietic stem cells(HSCs)are highly regulated by epigenetic modification,in which histone acetylation can activate or silence gene transcription.Histone deacetylase inhibitors(HDACIs)can inhibit the activity of histone deacetylase in HSCs to increase histone acetylation.A variety of HDACIs,such as trichostatin A and valproic acid,are used to expand HSCs in vitro,especially cord blood HSCs,combined with cytokines in serum-free culture to obtain more long-term repopulating cells.HDACIs promote the transcription of pluripotent genes related to stem cell self-renewal and inhibit the expression of genes related to differentiation,so as to promote the expansion and inhibit differentiation of HSCs.The expansion of cord blood HSCs by small molecular HDACIs in vitro is expected to improve the quantity of cord blood HSCs.The further research will focus on high-throughput screening for the most powerful HDACIs and the highly selective HDACIs,exploring the combination of epigenetic modifiers of different pathways.


Subject(s)
Epigenesis, Genetic , Fetal Blood , Hematopoietic Stem Cells , Histone Deacetylase Inhibitors/pharmacology , Valproic Acid/pharmacology
3.
Article in Chinese | WPRIM | ID: wpr-909474

ABSTRACT

Objective:To study the effect of senescence gene silent information regulator 6 (Sirt6) knockout on the brain of aged mice.Methods:Sirt6-flox transgenic mice were constructed, and the mouse brain tissue was specifically knocked out by Emx1-Cre tool mice.According to genotyping, 11 wild-type mice were selected as control group(WT group) and 10 Sirt6 gene konckout mice were selected as conditional knockout group(cKO group). Body size and body weight of the aged mice were measured and cerebral cortex thickness was measured by HE staining.Brain neurogenesis was analyzed with EdU markers.The expression of RNA-binding protein HuR and apoptosis-related protein Caspase-3 were detected by Western blot.Meanwhile, histone acetylation levels in the cortex were detected.Results:Sirt6 brain tissue-specific knocked out mice were successfully constructed.Compared with the brain tissue area((2.07±0.22) cm 2)and cortical thickness ((970.56±80.91) μm) of WT mice in the 12-month-old group, the brain tissue area ((1.61±0.14)cm 2) and cortical thickness ((822.88±53.94) μm) in Sirt6 cKO group were smaller, and the differences were statistically significant (both P<0.05). EdU incorporation into nerve cells showed that the number of EdU incorporation into periventricular nerve cells in cKO group was lower ((4.75±1.48)) than that in WT group ((10.29±1.93)). The difference was statistically significant ( P<0.001). In the experiment of 17 months age group, mice in cKO group were smaller in body size, lower in body weight ((29.00±1.08) g) and smaller in brain area ((1.54±0.55)cm 2)compared with WT group in body size, body weight ((35.25±4.17) g) and brain tissue area ((1.98±0.18) cm 2)(both P<0.05). The expression of Caspase-3 and HuR in cortical proteins of these two age groups decreased( t=2.95, 5.38, both P<0.05), and the expression of H3K9ac and H3K56ac increased( t=3.53, 2.78, both P<0.05), but the expression of Sirt1 homologous gene remained unchanged( t=1.26, P>0.05). Conclusion:The specific deletion of Sirt6 in brain tissue can lead to the decrease of brain neurogenesis in aged mice, and the aggravation of aging and the increase of apoptosis, which may be the reason for the thinning of cerebral cortex and brain tissue atrophy.The molecular mechanism is speculated to be related to the increase of acetylation level after Sirt6 knockout

4.
J Biosci ; 2020 Jan; : 1-12
Article | IMSEAR | ID: sea-214347

ABSTRACT

Epigenetic changes play a crucial role in sensing signals and responding to fluctuations in the extracellularenvironment. How the cellular micro-environment affects DNA damage response signalling in chromatincontext is not extensively studied. Histone acetylation is dynamic and very sensitive to changes in theextracellular environment. Existing literature on H3 lysine 56 acetylation (H3K56ac) levels upon DNA damagein mammals presents a conflicting picture. The occurrence of both increased and decreased H3K56ac uponDNA damage in our experiments led us to investigate the role of the micro-environment on H3K56ac. Here,we show that the global levels of H3K56ac increase as cells grow from low density to high density whileSIRT1 and SIRT6 expression decrease. Additionally, rising lactic acid levels increase H3K56ac. Our resultsshow that cell density and accumulation of metabolites affect dynamics of H3K56ac in response to DNAdamage. Upon DNA damage, H3K56ac increases in low density cells with low initial acetylation, whileacetylation decreases in high cell density cells. These results highlight that H3K56ac levels upon DNA damageare dependent on the metabolites in the extracellular milieu which impact chromatin structure by regulatingchromatin modifying enzymes. Accumulation of lactic acid at high cell density reflects conditions similar to thetumour micro-environment. As H3K56ac increases in tumours, lactic acid and low pH might alter H3K56ac intumours, leading to deregulated gene expression, contributing to tumour progression.

5.
Article in Chinese | WPRIM | ID: wpr-843121

ABSTRACT

Objective: To study the role of abnormal histone acetylation modification in the pathogenesis of IgA nephropathy (IgAN), and explore the pathogenesis of IgAN from the perspective of epigenetics. Methods: 30 patients with primary IgAN and 19 healthy controls were included. Of the 19 controls, 16 cases were used to collect blood samples and 3 cases were used to collect normal renal tissues. Peripheral venous blood was collected to extract mononuclear cells (PBMC) for detection. The levels of histone H3 and H4 acetylation in PBMC of IgAN group and healthy control group were detected by ELISA. Real-time PCR was used to detect the mRNA expressions of P300, CREBBP, HDAC1-3, HDAC7, HDAC8, C1GALT1 and ST6GALNAC2. The acetylation levels of histone H3 and H4 in promoter regions of C1GALT1 and ST6GALNAC2 were detected by chromatin immuneprecipitation (CHIP). The protein expression of HDAC1 and H3Ac was detected by immunofluorescence. T-test was used for statistical analysis. Results: Compared with the healthy control group, the acetylation levels of H3 and H4 in IgAN group were significantly higher than those in healthy control group (P=0.035, P=0.012);the mRNA expressions of P300, CREBBP, HDAC1, HDAC8 and ST6GALNAC2 were significantly increased in IgAN group (P=0.002, P=0.001, P=0.001, P=0.045 P=0.012); the mRNA expressions of HDAC2 and C1GALT1 were decreased significantly (P=0.035, P=0.008); the acetylation degree of H3 and H4 in C1GALT1 promoter region was significantly decreased (P=0.043, P=0.005), the degree of H3 and H4 acetylation in the promoter region of ST6GALNAC2 gene was increased significantly in IgAN group (P=0.038, P=0.021);immune fluorescent results of renal tissue indicated that the HDAC1 protein expression was increased obviously, and H3Ac protein expression was significantly reduced in the renal tissue of IgAN patiegts. Conclusion: Abnormal acetylation modification exists in IgAN patients. Histone acetylation modification may participate in the pathogenesis of IgAN by regulating the expression of glycosylase gene.

6.
Braz. j. med. biol. res ; 53(10): e9861, 2020. graf
Article in English | 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
7.
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
8.
Article in Chinese | WPRIM | ID: wpr-843414

ABSTRACT

Objective • To investigate the effect of anemarrhena saponin (ZMS) on mRNA level of brain-derived neurotrophic factor (BDNF) and relevant mechanism in oxidative stress damage of SH-SY5Y cells. Methods • SH-SY5Y cells treated with H2O2 were chosen as cell models of oxidative stress. Cell viability was determined using cell counting kit-8 (CCK-8). The mRNA levels of BDNF and its important transcripts were detected by quantitative real-time PCR (qPCR). The histone deacetylases (HDACs) activity fluorescence quantification assay kit was used to measure the effect of ZMS on HDACs activity. Western blotting was used to detect the protein expression levels of acetylated histone H3, acetylated histone H4, specific acetylation site-related proteins, and HDAC1/2/3. Results • qPCR showed that ZMS could increase the mRNA levels of BDNF and its transcript in the cell models. Western blotting showed that ZMS pretreatment could increase the protein levels of acetylated histone H3, acetylated histone H4 and acetylated histone H3K14, and there was no significant effect on protein levels of HDAC1/2/3. In addition, HDACs activity fluorescence quantification assay kit showed that ZMS could inhibit HDACs activity significantly. Conclusion • ZMS can increase the mRNA levels of BDNF and its transcript in oxidative stress damage cell models, which may be related to the regulation of histone acetylation level

9.
Article in Chinese | WPRIM | ID: wpr-817792

ABSTRACT

@#【Objective】To investigate the impact of long- term storage time on epigenetic modification of histone in human cleavage stage embryos.【Methods】According to the length of storage time,donated embryos after slow-freezing were divided into 3 groups :6-year group ,9-year group ,and 12-year group ,while the control group consisted of donated fresh embryos. Immunocytochemistry was performed to compare the expression levels of HDAC1, H3K9ac, H3K4me3 ,and H3K9me3 among 4 groups. Transcription levels of HDAC1 ,SUV39H1 ,SETDB1 ,and KDM5A were analyzed through Single-Cell qRT-PCR.【Results】The relative abundances of HDAC1 and SUV39H1 mRNA showed no significant differences among 4 groups(P > 0.05). SETDB1 exhibited a climbing pattern as storage time increased,but no significant difference was observed(P > 0.05). There were no differences in H3K9 trimethylation and H3K9 methylation among 4 groups. However ,the expression level of KDM5A increased with the increasing storage time(P < 0.05).【Conclusions】 Storage time did not affect the expression of deacetylase HDAC1,methylase SUV39H1 and SETDB1. H3K9ac/me3 and H3K4me3 also exhibited no significant difference as the storage time increases. However ,the increasing storage length might induce the elevating expression of demethylase KDM5A,which may be associated with inhibition of embryonic transcription.

10.
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
11.
Braz. j. med. biol. res ; 51(12): e7437, 2018. tab, graf
Article in English | LILACS | ID: biblio-974252

ABSTRACT

Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.


Subject(s)
Humans , DNA Methylation/genetics , RNA, Untranslated/genetics , Epigenesis, Genetic/genetics , Histone Code/genetics , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/genetics , Pulmonary Artery/pathology , Down-Regulation/genetics , Up-Regulation/genetics , Ubiquitination/genetics , Molecular Targeted Therapy , Hypertension, Pulmonary/therapy
12.
Article in Chinese | WPRIM | ID: wpr-851916

ABSTRACT

Objective Based on quantitative proteomics analysis and molecular biology experimental verification, the regulatory mechanism of ginsenoside Rd on histone H3 acetylation levels was elucidated. Methods The effects of ginsenoside Rd on the dynamic changes of proteome of HEK293T cells were detected by.stable isotope labeling with amino acid (SILAC) technique and LC-MS/MS; Quantitative proteomics database analysis was used to monitor the changes in histone acetyltransferase HATs and histone deacetylase HDACs expression levels. Western blotting and qRT-PCR were used to verify the changes of related protein expression and transcriptional level. Gene knockdown experiments were performed using siRNAs to determine the role of ginsenoside Rd in regulating the level of acetyl modifications at histone H3K9 and K18 sites. Results The histone H3K9ac, H3K18ac expression levels in HEK293T cells decreased after ginsenoside Rd treatment, but the P300 catalytic modification of these two sites did not change significantly; At the same time, ginsenoside Rd up-regulated the transcription and expression of HDAC2, and siHDAC2 treatment reversed the down-regulation effects of ginsenoside Rd on H3K9ac and H3K18ac in HEK293T cells. Conclusion Ginsenoside Rd down-regulates the acetylation level of lysine at histone H3K9 and K18 sites by up-regulating HDAC2, thereby affecting transcriptional activation of downstream genes.

13.
Article in Chinese | WPRIM | ID: wpr-704176

ABSTRACT

Objective To investigate the effect of sevoflurane anesthesia on learning and memory in mice and the relationship with histone acetylation. Methods Thirty-six adult male C57BL/6 mice were ran-domly divided into control group(mice inhaled 95% O2 for 6 h), sevoflurane (Sevo) group (1. 5% Sevo group, 2% Sevo group, 3% Sevo group:mice inhaled 1. 5%, 2% and 3% sevoflurane for 6 h respectively) , sevoflurane + SAHA (Sevo + SAHA) group (mice were intraperitoneally injected with histone deacetylase inhibitor SAHA ( 25 mg/kg) . And 1 h later, 3% Sevo was inhaled continuously for 6 hours. ) and SAHA group(mice were intraperitoneally injected with histone deacetylase inhibitor SAHA (25 mg/kg)). The abil-ity of learning and memory in mice was estimated by Morris water maze. The expression levels of Ac-H3, BDNF and Syt-I protein in the hippocampus were detected by Western blot. Results In Morris water maze, 3% sevoflurane anesthesia significantly prolonged the escape latency((46. 91±1. 84)s),and significantly decreased the ratio of target time((35. 84±5. 40)%) compared with that of control group((23. 46±2. 67)s, (49. 74±4. 91)%,P<0. 05). Compared with 3% Sevo group,the ratio of target time in Sevot+SAHA group ((46. 86±4. 37)%) was increased(P<0. 05). Moreover,3% sevoflurane anesthesia significantly decreased the expression levels of Ac-H3 (10. 23±2. 45),BDNF (6. 72±1. 21) and Syt-I (8. 25±2. 11) in the hippo-campus compared with that of control group((15. 45±2. 58),(10. 17±1. 45) and (15. 02±3. 38),P<0. 05) . However,pre-administration of the histone deacetylase inhibitor SAHA significantly increased the ra-tio of target time in Morris water maze,and improved the expression levels of Ac-H3 (14. 06±2. 79),BDNF (10. 13±1. 06) and Syt-I (14. 16±3. 66) in Sevo+SAHA group compared with that of Sevo group (P<0. 05) . Conclusion The high dose of sevoflurane anesthesia can induce learning and memory impairment through the inhibitation of histone acetylation in the hippocampus.

14.
Article in Chinese | WPRIM | ID: wpr-703355

ABSTRACT

Objective To investigate the effect and molecular mechanism of botulinum neurotoxin serotype A (BoNT/A) heavy chain on neuron regeneration. Methods Cell culture, rats, immunofluorescence, SDS-PAGE and western blot, etc. were adopted in this study to explore the alterations of histone-3 acetylation (acetyl-H3 ) by local treatment of BoNT/A heavy chain to spinal cord injury (SCI) in rats (in vivo) or by adding it into cell culture (in vitro). Meanwhile, the relevance of acetyl-H3 to neurite out-growth based on SCI and cell culture with BoNT/A heavy chain application was approached as well. Results The application of BoNT/A heavy chain to cultured Neuro-2a cells increased the level of H3 acetylation. The increase of H3 acetylation was paralleled with the growth of neuritogenesis. Also, the neuronal treatment of BoNT/A heavy chain to SCI promoted the re-growth of neuronal processes surrounding the lesions. The growth of neuronal processes was positively correlated to the level of H3 acetylation. During the periods of BoNT/A heavy chain treatment in vivo or in vitro, the increase of H3 acetylation showed two peaks. Conclusions BoNT/A heavy chain increased the H3 acetylation, which might be one of its neuritogenic mechanisms.

15.
Article in Chinese | WPRIM | ID: wpr-701259

ABSTRACT

Objective To establish an model of fluorosis with human primary osteoblasts in vitro and to detect the influences of different doses of sodium fluoride (NaF) on histone acetylation of CyclinD1,cyclindependent kinases 4 (CDK4) gene in human osteoblasts,then to explore the molecular mechanism of skeletal fluorosis from epigenetic perspective of the cell cycle regulation related genes.Methods Human primary osteoblasts from bone tissues of trauma surgery healthy people (car accident) were isolated by enzyme digestion and identified.The osteoblasts were treated with 0,125,250,500 and 1 000 μmol/L NaF for 72 h.The level of histone acetylation (H3K9,H3K14,H4K12,H4K16) in the transcription regulatory region (ChIP1 region) and in the coding region (ChIP2 region) of CyclinD1 and CDK4 genes were detected by quantitative chmmatin immuno-precipitation (Q-ChIP).Results ①After human osteoblasts were treated with 0,125,250,500 and 1 000 μmol/L NaF,respectively,the levels of histone acetylation of H3K9 in ChIP1 transcription regulatory region of CyclinD1 gene were 1.152 ± 0.104,1.174 ± 0.187,1.090 ± 0.176,1.170 ± 0.197 and 1.147 ± 0.097,respectively,the differences were not statistically significant (F =0.524,P > 0.05);the average levels of histone acetylation of H3K14 were 1.495 ± 0.117,1.465 ± 0.069,1.470 ± 0.187,1.760 ± 1.089 and 1.341 ± 0.443,the differences were not statistically significant (F =0.841,P > 0.05);the levels of histone acetylation of H4K12 were 1.239 ± 0.286,0.702 ± 0.063,0.765 ± 0.370,1.011 ± 0.321 and 1.319 ± 0.026,the differences were not statistically significant (F =2.329,P > 0.05);the levels of histone acetylation of H4K16 were 1.452 ± 0.217,1.621 ± 0.165,1.462 ±0.090,1.510 ± 0.146 and 1.564 ± 0.154,the differences were not statistically significant (F =0.123,P > 0.05).②The levels of histone acetylation of H3K9 in ChIP1 transcription regulatory region of CDK4 were 1.472 ± 0.163,1.580 ± 0.161,1.585 ± 0.132,1.451 ± 0.136 and 1.560 ± 0.039,the differences were not statistically significant (F =0.461,P > 0.05);the levels of histone acetylation of H3K14 were 0.919 ± 0.149,0.900 ± 0.059,0.911 ±0.162,0.663 ± 0.049 and 0.841 ± 0.122,the differences were not statistically significant (F =0.974,P > 0.05);the levels of histone acetylation of H4K12 were 0.456 ± 0.142,0.911 ± 0.126,0.969 ± 0.185,1.110 ± 0.146 and 0.931 ± 0.141,the differences were not statistically significant (F=5.459,P > 0.05);the levels of histone acetylation of H4K16 were 1.315 ± 0.083,1.374 ± 0.153,1.423 ± 0.055,1.300 ± 0.132 and 1.385 ± 0.696,the differences were not statistically significant (F =1.663,P > 0.05).③The differences of histone acetylation levels of H3K9,H3K14,H4K12 and H4K16 in ChIP2 coding region of CyclinD1 and CDK4 genes were not statistically significant between NaF treatment groups (F =0.392,0.823,0.999,0.397,0.705,0.049,1.065,0.196,P > 0.05).Conclusion The histone acetylation of CyclinD1 and CDK4 may not be involved in the transcriptional regulation in human primary osteoblasts treated with fluoride.

16.
Clinical Medicine of China ; (12): 176-179, 2018.
Article in Chinese | WPRIM | ID: wpr-706646

ABSTRACT

Obstructive sleep apnea syndrome is a kind of common sleep and respiratory disorder with unknown cause. Epigenetics is a branch of genetics that studies the genetic variation of gene expression under the condition of unchanged nucleotide sequence, including DNA methylation, histone modification, chromatin remodeling,and non coding RNA regulation.

17.
Article in Chinese | WPRIM | ID: wpr-777828

ABSTRACT

Objective@#To investigate the histone acetylation level and histone deacetylase (HDAC) activity of peripheral blood CD4+ T lymphocytes in patients with oral lichen planus (OLP). @*Methods @#Twenty-three OLP patients were selected from August 2016 to January 2017 from the Stomatological Hospital, Southern Medical University. The diagnosis was confirmed by pathology, and the lesions were divided into a nonerosive OLP group (11 cases) and an erosive OLP group (12 cases). Ten healthy sex- and age-matched volunteers served as controls. Immunomagnetic beads were used to separate CD4+ T lymphocytes, and histones and nucleoproteins were extracted. The global histone H3/H4 acetylation levels and HDAC activity of CD4+ T lymphocytes from all subjects were detected by ELISA. The differences between the OLP and control groups were statistically analyzed. @*Results@#Global histone H3 hypoacetylation was observed in the OLP group compared with the control group (u = -2.410, P = 0.012). However, there was no significant difference in the serum CD4+ T lymphocyte histone H4 acetylation level between the OLP and control group (u = -1.412, P = 0.158). HDAC activity was significantly higher in the OLP group than in the healthy control group (F = 5.749, P = 0.023), and much higher HDAC activity was observed in the erosive group than in the nonerosive (P = 0.014) and healthy control groups (P = 0.001). The degree of histone H3 acetylation correlated negatively with increased HDAC activity in the OLP group (rs = -0.771, P < 0.001). There was no correlation between the level of histone H3 acetylation and HDAC activity in the healthy control group (rs = 0.382,P = 0.276). The histone H4 acetylation level in the OLP group showed no correlation with HDAC activity (rs = 0.149, P = 0.498), and the histone H4 acetylation level in the control group also showed no correlation with HDAC activity (rs = 0.527, P = 0.117).@*Conclusion @#Abnormal histone acetylation of CD4+ T lymphocytes in the peripheral blood of patients with OLP was identified and could be related to HDAC activity, suggesting that the epigenetic modification of histone acetylation may play a role in the pathogenesis of OLP.

18.
Article in Chinese | WPRIM | ID: wpr-664846

ABSTRACT

Objective To investigate the effects of sodium butyrate on ethanol-seeking behavior and H3K9 acetylation levels in NMDA receptor 2B subunit(NR2B) promoter region in the hippocampus of Wistar rats.To explore the epigenetic mechanism underlying ethanol-seeking behavior.Methods According to random number table,48 male Wistar rats were divided into saline group,sodium butyrate group,ethanol group and sodium butyrate + ethanol group,with 12 rats in each group and administered by intraperitioneal injection respectively.Conditioned place preference (CPP)was used to evaluate the ethanol-seeking behavior.Using Western-blot,real-time PCR and chromatin immunoprecipitation assays,the expression of NR2B protein,NR2BmRNA and the relative level acetylated H3K9 in NR2B promoter region in the hippocampus were determined respectively.Results The CPP test and the CPP score in each group were different (P< 0.05).Compared with the CPP test(261.1 ± 102.2) and the CPP score(48.5±94.6) of saline group,the CPP test ((406.8±109.2),(502.7±72.89)) and the CPP score((198.2± 119.4),(277.5±76.2)) of ethanol group and sodium butyrate + ethanol group were significantly higher(P<0.05),the CPP test(193.4±93.8) and the CPP score (9.7±94.0)of sodium butyrate group were not significantly different(P>0.05).Compared with the ethanol group,CPP test of sodium butyrate + ethanol group was significantly higher(P<0.05).The expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus in each group were different (P< 0.05).Compared with the expression of NR2B protein (1.00 ± 0.28),NR2BmRNA(1.00±0.14) and H3K9 acetylation in NR2B promoter region(1.00±0.25)in the hippocampus of saline group the expression of NR2B protein((1.40±0.34),(1.79±0.30)),NR2BmRNA((1.26±0.16),(1.50±0.08)) and aeetylated level H3K9 in NR2B promoter region ((1.68±0.16),(2.35±0.45)) of ethanol group and sodium butyrate ± ethanol group were significantly higher(P<0.05).The expression of NR2B protein(0.85±0.24),NR2BmRNA(1.05±0.13) and acetylated level H3K9 in NR2B promoter region(0.96±0.41) of sodium butyrate group were not significantly different(P>0.05).Compared with the ethanol group,the expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus of ethanol group,these of sodium butyrate + ethanol group were significantly higher (P<0.05).The CPP score were positively correlated with the expression of NR2B protein (r=0.474,P<0.05).The expression of NR2B protein were positively correlated with the expression of NR2BmRNA (r=0.468,P<0.05).The expression of NR2BmRNA were positively correlated with the expression of H3K9 acetylation in NR2B promoter region(r=0.596,P<0.05),and the CPP score were positively correlated with the expression of H3K9 acetylation in NR2B promoter region (r=0.542,P<0.05).Conclusion The increasing acetylation level of H3K9 in NR2B promoter region in the hippocampus may be one of the epigenetic mechanisms of promoting ethanolseeking behavior,and H3K9 deacetylation in NR2B promoter region in the hippocampus is likely to be a new target for controlling ethanol dependence.

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Article in Chinese | WPRIM | ID: wpr-612658

ABSTRACT

Objective To investigate the effects of p300/CBP on histone acetylation of Foxp3 gene and its roles in the immunological pathogenesis of Kawasaki disease (KD).Methods Forty-six children with KD and twenty-eight age-matched health children were consented to participate in this study.Co-immunoprecipitation and real-time PCR were performed to detect Foxp3-associated acetylation levels of histone H4 and binding abilities of p300, CBP, pSmad3 (phosphorylated mothers against decapentaplegic homolog 3) and NF-AT (nuclear factor of activated T cells) with Foxp3 gene in CD4+ T cells.The percentages of CD4+CD25high Foxp3+ cells (Treg) and the expression of Foxp3, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), p300, CBP, TGF-βRⅡ (transforming growth factor β receptor Ⅱ) and pLAT1 at protein level were analyzed by flow cytometry.Quantitative real-time PCR was used to measure the expression of Foxp3, IL-10, TGF-β, TGF-βRⅠ, Egr-1 (early growth response protein 1), RARα (retinoic acid receptor α) and PLCγ1 (phospholipase C-γ1) in Treg cells at mRNA level.Plasma concentrations of TGF-β and retinol acid (RA) were measured by enzyme-linked immunosorbent assay.Results (1) The percentages of Treg cells, levels of Foxp3 and molecules associated with suppressive function of Treg cells (TGF-β, IL-10 and CTLA4), acetylation levels of histone H4 associated with promoter, conserved non-coding DNA sequence 1 (CNS1) and CNS2 of Foxp3 gene decreased remarkably during acute KD (P0.05).(2) The levels of p300 and CBP in Treg cells and their binding abilities with Foxp3 gene were down-regulated significantly during acute KD (P0.05).Conclusion Hypoacetylation of histone H4 associated with Foxp3 gene caused by insufficient expression of p300/CBP and their impaired binding abilities might be involved with immune dysfunction in KD.IVIG therapy regulates the expression of p300/CBP and their binding abilities with Foxp3 gene through up-regulating TGF-β signal.

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Chinese Pharmacological Bulletin ; (12): 52-57,58, 2017.
Article in Chinese | WPRIM | ID: wpr-606239

ABSTRACT

Aim To study the role of histone acetyla-tion and its involvement in the depression-like behav-iors of rats induced by chronic unpredictable stress (CUS ). Methods Thirty male Sprague Dawley (SD ) rats were randomly divided into control group and model group.The method of solitary condition with CUS for consecutive 28 days was used to establish the rat depression model.The open-field test (OFT)and the forced swimming test (FST)were used to evaluate the depressive behaviors of rats;the real time PCR was used to detect the change of HDAC2 mRNA, and Western blot was used to determine the protein expres-sions of H3,H4,acH3 and acH4 in the prefrontal cor-tex and hippocampus of rats.Results Model group showed obvious depression-like behaviors with decrea-sing locomotive activity in OFT (P <0.01 )and in-creasing immobility time in FST (P<0.01),up-regu-lating the mRNA and protein expression of HDAC2 (P<0.0 1 ),and down-regulating the protein expression of acH3 and acH4 (P<0.01)in the prefrontal cortex and hippocampus significantly,compared with control group.Conclusion The mechanism of depressive be-haviors of rats induced by CUS may be associated with down-regulating the level of histone acetylation modifi-cation.

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