OBJECTIVE: This study aims to investigate the mechanism of K (lysine) acetyltransferase 2A (KAT2A) regulation and control on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The expression levels of KAT2A in PDLSCs were compared from each generation of the normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A gene interference on the osteogenic differentiation of PDLSCs were also detected. In addition, the influences of the KAT2A gene interference to the canonical Wnt pathway and ligands were detected. The upstream and down-stream relationships between KAT2A and canonical Wnt pathway were also determined. RESULTS: The decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each generation was compared with that in PDLSCs from the healthy tissue, and the difference was statistically significant (P<0.05). When the KAT2A gene was disrupted, the osteogenesis ability of PDLSC was declined, and the difference was statistically significant (P<0.05). The canonical Wnt pathway was activated, and the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was unaffected. CONCLUSIONS The KAT2A expression in PDLSCs was decreased because of perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic differentiation of the cells.
Acetyltransferases ; Cell Differentiation ; Cells, Cultured ; Histone Acetyltransferases ; metabolism ; Humans ; Lysine ; Osteogenesis ; Periodontal Ligament ; metabolism ; Periodontitis ; metabolism ; Stem Cells ; Wnt Signaling Pathway

Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.
Acetylation ; Acute Kidney Injury ; Histone Acetyltransferases/metabolism* ; Histone Deacetylases/metabolism* ; Humans ; Protein Processing, Post-Translational

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.
Acetylation ; Animals ; Histone Acetyltransferases ; Histones ; metabolism ; Methylation ; Mice ; Protein Processing, Post-Translational

No abstract available.
Acetyltransferases/metabolism ; Animal ; Carrier Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Human ; Nuclear Proteins/metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Repressor Proteins/metabolism*n ; Trans-Activators/metabolism* ; Transcription Factors/metabolism

In most insects, polyunsaturated fatty acids (PUFAs) are mainly polyunsaturated fatty acids with a carbon-chain length less than 18 carbon atoms, hardly any long-chain polyunsaturated fatty acids such as C20 and C22 that are more valuable and bioactive. This study, by using Drosophila melanogaster (Fruit fly) as a model organism, optimized the Δ6-fatty acid elongase enzyme Elovl5 gene from mice and transferred it to fruit flies for expression. Vectors containing Elovl5 gene were successfully injected into drosophila embryo through the microscopic injection. There were enhanced green fluorescent proteins expressed in the whole developmental stage of Drosophila be means of fluorescence microscope. At the same time, expression of Elovl5 gene significantly contributed to the transformation of fruit flies C18-polyunsaturated fatty acids in the body towards the biosynthesis of longer-chain polyunsaturated fatty acids. The transgenic fruit fly model rich in long-chain polyunsaturated fatty acids such as C20 and C22 were obtained, providing a basis for further research on biosynthesis of polyunsaturated fatty acids in fruit flies.
Acetyltransferases/genetics* ; Animals ; Drosophila melanogaster/genetics* ; Fatty Acid Elongases/metabolism* ; Fatty Acids/genetics* ; Gene Transfer Techniques ; Mice

Preparation of a pure autoantigen by way of recombinant DNA technology has an important value in an accurate diagnosis or prognosis of an autoimmune disease. BCOADC-E2 subunit, a mitochondrial protein, has been known to be the autoantigen of primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, as well as idiopathic dilated cardiomypathy (IDCM), a chronic autoimmune heart disease. Recombinant form of this molecule had been expressed in E. coli but with low yield and severe degradation. Furthermore, sera from IDCM patients failed to recognized BCOADC-E2 molecule produced in prokaryotic expression system. In this study, a recombinant bovine BCOADC-E2 fusion protein has been expressed in insect cells using baculovirus expression system and analyzed anti-BCOADC-E2 reactivity in sera from patients with PBC or with IDCM. Optimal production of the recombinant fusion protein has been achieved at 20 multiplicity of infection (MOI), and the protein was affinity-purified using metal-binding resins. The affinity-purified BCOADC-E2 protein was successfully recognized by sera from PBC patients, but not by sera from IDCM patients suggesting that the different auto-immune response against BCOADC-E2 is needed to be elucidated in terms of epitope recognition.
Acetyltransferases/metabolism ; Acetyltransferases/immunology ; Acetyltransferases/genetics* ; Animal ; Baculoviridae/genetics ; Cardiomyopathy, Congestive/immunology ; Cattle ; Human ; Immune Sera ; Insects/cytology* ; Ketone Oxidoreductases/metabolism ; Ketone Oxidoreductases/immunology* ; Ketone Oxidoreductases/genetics* ; Liver Cirrhosis, Biliary/immunology ; Multienzyme Complexes/metabolism ; Multienzyme Complexes/immunology* ; Multienzyme Complexes/genetics* ; Protein Engineering/methods ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/immunology ; Recombinant Proteins/genetics*

During the past few years, gene expression studies have shown that the perturbation of transcription frequently results in neuronal dysfunction in polyglutamine (PolyQ) diseases such as Huntington's disease (HD). Histone deacetylases (HDACs) act as repressors of transcription through interaction with co-repressor complexes, leading to chromatin remodelling. Aberrant interaction between PolyQ proteins and regulators of transcription could be one mechanism by which transcriptional dysregulation occurs. Here, the authors discuss the possible mechanism of transcriptional dysfunction in PolyQ disease, including the effect of histone acetyltransferases (HATs) and HDACs on pathogenesis, and the potential therapeutic pathways through which histone deacetylase inhibitors (HDACIs) might act to correct the aberrant transcription observed in HD and other PolyQ diseases.
Animals ; Histone Acetyltransferases ; genetics ; metabolism ; Histone Deacetylase Inhibitors ; therapeutic use ; Histone Deacetylases ; genetics ; metabolism ; Humans ; Huntington Disease ; drug therapy ; enzymology ; metabolism ; Peptides ; metabolism

Treatment of latent tuberculosis infection remains an important goal of global TB eradication. To this end, targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive. Arylamine N-acetyltransferase (NAT) represents such a target as it is, along with the enzymes encoded by the associated gene cluster, essential for mycobacterial survival inside macrophages and involved in cholesterol degradation. Cholesterol is likely to be the fuel for M. tuberculosis inside macrophages. Deleting the nat gene and inhibiting the NAT enzyme prevents survival of the microorganism in macrophages and induces cell wall alterations, rendering the mycobacterium sensitive to antibiotics to which it is normally resistant. To date, NAT from M. marinum (MMNAT) is considered the best available model for NAT from M. tuberculosis (TBNAT). The enzyme catalyses the acetylation and propionylation of arylamines and hydrazines. Hydralazine is a good acetyl and propionyl acceptor for both MMNAT and TBNAT. The MMNAT structure has been solved to 2.1 Å resolution following crystallisation in the presence of hydralazine and is compared to available NAT structures. From the mode of ligand binding, features of the binding pocket can be identified, which point to a novel mechanism for the acetylation reaction that results in a 3-methyltriazolo[3,4-a]phthalazine ring compound as product.
Acetyltransferases ; metabolism ; Arylamine N-Acetyltransferase ; chemistry ; genetics ; metabolism ; Catalysis ; Catalytic Domain ; Crystallization ; Mycobacterium ; enzymology ; metabolism ; Mycobacterium marinum ; enzymology ; Mycobacterium tuberculosis ; enzymology ; genetics ; metabolism ; Protein Binding

PURPOSE: The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters. MATERIALS AND METHODS: Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay. RESULTS: The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01). CONCLUSION: Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.
Acetylation ; Adult ; DNA Fragmentation ; Epigenesis, Genetic ; Histone Acetyltransferases/*metabolism ; Histones/*metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Protein Processing, Post-Translational ; Semen Analysis ; Spermatozoa/*metabolism

OBJECTIVETo explore the role of histone H3 acetylation in cleft palate induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice, and its mechanism.

METHODSOn gestation day 10 (GD10), 36 pregnant mice were randomly divided into two groups as the treated group(n = 18) and the control group( n = 18). The mice in the treated group received intragastric administration with TCDD 28 μg/kg, while the mice in the control group received equivalent corn oil. The pregnant mice were sacrificed on GD13. 5, GD14. 5 and GD15. 5, collecting fetal palates to determine the activities of histone acetyltransferases (HATs) by Colorimetric and the expression level of acetylated histone H3 (Acetylated histone H3, Ac-H3) by Western-blot.

RESULTSThe activity of HATs was 0.409 7 ± 0.0147, 0.522 3 ± 0.017 1 and 0.643 5 ± 0.013 9 in control group on GD13.5, GD14.5 and GD15.5; 0.865 0 ± 0.0129, 0.719 1 ± 0.017 8 and 0.551 2 ± 0.016 8 in TCDD group. The activity of HATs in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference between the two groups (t = - 56. 932, t = - 19. 516, P < 0.01); however, the activity of HATs in TCDD group was significantly lower than that in control group on GD15. 5 (t = 10. 382, P < 0.01). The expression level of Ac-H3 was 0.745 0 ± 0.113 5, 1.055 9 ± 0.249 4 and 1.795 5 ± 0.081 9 in control group on GD13. 5, GD14. 5 and GD15. 5; while 1.4490 ± 0. 1460, 1. 641 8 ± 0.099 7 and 1. 512 1 ± 0. 150 2 in TCDD group. The expression of Ac-H3 in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference( t = -6. 593, -3. 779, P <0. 01, P <0.05) ; However, the expression of Ac-H3 in TCDD group was statistically lower than that in control group (t = 2. 870, P <0. 05).

CONCLUSIONThe acetylation of histone H3 was involved in the cleft palate of C57BL/6J mice induced by TCDD, which may be one of the mechanisms in TCDD-induced cleft palate.

Acetylation ; drug effects ; Acetyltransferases ; metabolism ; Animals ; Cleft Palate ; chemically induced ; metabolism ; Dioxins ; Female ; Fetus ; Histones ; metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; Pregnancy ; Random Allocation ; Teratogens