• Journal of Microbiology and Biotechnology
• /
• v.27 no.1
• /
• pp.189-196
• /
• 2017

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with formation of Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Replication and transcription activator (RTA) genes are expressed upon reactivation of KSHV, which displays a biphasic life cycle consisting of latent and lytic replication phases. RTA protein expression results in KSHV genome amplification and successive viral lytic gene expression. Transcriptional activity of viral lytic genes is regulated through epigenetic modifications. In Raji cells latently infected with Epstein-Barr virus, various modifications, such as acetylation and methylation, have been identified at specific lysine residues in histone H4 during viral reactivation, supporting the theory that expression of specific lytic genes is controlled by histone modification processes. Data obtained from chromatin immunoprecipitation and quantitative real-time PCR analyses revealed alterations in the H4K8ac and H4K20me3 levels at lytic gene promoters during reactivation. Our results indicate that H4K20me3 is associated with the maintenance of latency, while H4K8ac contributes to KSHV reactivation in infected TREx BCBL-1 RTA cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.1
• /
• pp.23-33
• /
• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• Tuberculosis and Respiratory Diseases
• /
• v.80 no.3
• /
• pp.255-264
• /
• 2017

Background:N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH) to N-acetyl INH through a process of acetylation, and confers low-level resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB, NAT2 in humans performs the same function of acetylation. Rapid acetylators, may not respond to INH treatment efficiently, and could be a potential risk factor, for the development of INH resistance in humans. Methods: To understand the contribution of NAT of MTB and NAT2 of humans in developing INH resistance using in silico approaches, in this study, the wild type (WT) and mutant (MT)-NATs of MTB, and humans, were modeled and docked, with substrates and product (acetyl CoA, INH, and acetyl INH). The MT models were built, using templates 4BGF of MTB, and 2PFR of humans. Results: On the basis of docking results of MTB-NAT, it can be suggested that in comparison to the WT, binding affinity of MT-G207R, was found to be lower with acetyl CoA, and higher with acetyl-INH and INH. In case of MT-NAT2 from humans, the pattern of score with respect to acetyl CoA and acetyl-INH, was similar to MT-NAT of MTB, but revealed a decrease in INH score. Conclusion: In MTB, MT-NAT revealed high affinity towards acetyl-INH, which can be interpreted as increased formation of acetyl-INH, and therefore, may lead to INH resistance through inactivation of INH. Similarly, in MT-NAT2 (rapid acetylators), acetylation occurs rapidly, serving as a possible risk factor for developing INH resistance in humans.

• The Plant Pathology Journal
• /
• v.36 no.4
• /
• pp.314-322
• /
• 2020

Interplay between histone acetylation and deacetylation is one of the key components in epigenetic regulation of transcription. Here we report the requirement of MoHDA1-mediated histone deacetylation during asexual development and pathogenesis for the rice blast fungus, Magnaporthe oryzae. Structural similarity and phylogenetic analysis suggested that MoHDA1 is an ortholog of Saccharomyces cerevisiae Hda1, which is a representative member of class II histone deacetylases. Targeted deletion of MoHDA1 caused a little decrease in radial growth and large reduction in asexual sporulation. Comparison of acetylation levels for H3K9 and H3K14 showed that lack of MoHDA1 gene led to significant increase in H3K9 and H3K14 acetylation level, compared to the wild-type and complementation strain, confirming that it is a bona fide histone deacetylase. Expression analysis on some of the key genes involved in asexual reproduction under sporulation-promoting condition showed almost no differences among strains, except for MoCON6 gene, which was up-regulated more than 6-fold in the mutant than wild-type. Although the deletion mutant displayed little defects in germination and subsequent appressorium formation, the mutant was compromised in its ability to cause disease. Wound-inoculation showed that the mutant is impaired in invasive growth as well. We found that the mutant was defective in appressorium-mediated penetration of host, but did not lose the ability to grow on the media containing H₂O₂. Taken together, our data suggest that MoHDA1-dependent histone deacetylation is important for efficient asexual development and infection of host plants in M. oryzae.

• Korean Journal of Poultry Science
• /
• v.17 no.3
• /
• pp.217-223
• /
• 1990

This study was undertaken to find out the changes of chemically modified egg albumen grl after heat treatment at $95^{\circ}C$ for 30 minutes or at $120^{\circ}C$ for 30 minutes. Acetylation and succinylation increased the hardness of egg albumen gel, it was rather higher at high heat treatment($120^{\circ}C$, 30min.) than at low heat treatment($95^{\circ}C$, 30min). The cohesiveness of egg albumen gel was improved remarkably by succinylation and maleylation at both low and high heat treatment. The lightness and yellowness of egg albumen gel were decreased by chemical modification. Initial heat denaturation temperature of egg albumen was increased by 11$^{\circ}C$ by acetylation, by $12.5^{\circ}C$ by maleylation and by ,$14.5^{\circ}C$ by succinylation.

• Journal of the Korean Wood Science and Technology
• /
• v.31 no.5
• /
• pp.57-64
• /
• 2003

Small cherry specimens modified with acetic anhydride and formaldehyde vapor phase were weathered by outdoor exposure and accelerated conditioning in a climate chamber. The effects of the chemical modification were evaluated by measuring their weight percentage gains (WPG), hygroscopicity and color differences before and after weathering. The average WPGs of the 72 hour acetylated and formaldehyde-treated specimens were 8.1 and 15.7%, respectively. After outdoor exposure for more than 2 months, the acetylated specimens lost weights by only 1.5%, but the formaldehyde-treated did much more than the formers. It was revealed that acetylation reduced the hygroscopicity and discoloration of wood while formaldehyde treatment didn't. Moreover the longer is the formaldehyde treatment time the more degraded after weathering. It was concluded that the vapor-phase acetylation could be applied for improving the dimensional stability of old wooden blocks.

• Molecules and Cells
• /
• v.45 no.11
• /
• pp.855-867
• /
• 2022

For proper function of proteins, their subcellular localization needs to be monitored and regulated in response to the changes in cellular demands. In this regard, dysregulation in the nucleocytoplasmic transport (NCT) of proteins is closely associated with the pathogenesis of various neurodegenerative diseases. However, it remains unclear whether there exists an intrinsic regulatory pathway(s) that controls NCT of proteins either in a commonly shared manner or in a target-selectively different manner. To dissect between these possibilities, in the current study, we investigated the molecular mechanism regulating NCT of truncated ataxin-3 (ATXN3) proteins of which genetic mutation leads to a type of polyglutamine (polyQ) diseases, in comparison with that of TDP-43. In Drosophila dendritic arborization (da) neurons, we observed dynamic changes in the subcellular localization of truncated ATXN3 proteins between the nucleus and the cytosol during development. Moreover, ectopic neuronal toxicity was induced by truncated ATXN3 proteins upon their nuclear accumulation. Consistent with a previous study showing intracellular calcium-dependent NCT of TDP-43, NCT of ATXN3 was also regulated by intracellular calcium level and involves Importin α3 (Imp α3). Interestingly, NCT of ATXN3, but not TDP-43, was primarily mediated by CBP. We further showed that acetyltransferase activity of CBP is important for NCT of ATXN3, which may acetylate Imp α3 to regulate NCT of ATXN3. These findings demonstrate that CBP-dependent acetylation of Imp α3 is crucial for intracellular calcium-dependent NCT of ATXN3 proteins, different from that of TDP-43, in Drosophila neurons.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.29-38
• /
• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.11 no.2
• /
• pp.118-125
• /
• 2001

Recently, biochemical analysis using hemoglobin adduct is frequently performed to evaluate the exposure to chemical carcinogens. However, data on the effect of co-exposure with other chemicals on hemoglobin adduct formation are seldom provided. The objective of this study is to evaluate the effects of pretreatment of ethanol(EtOH) and phenobarbital(PB), which are known to affect metabolism of xenobiotics, on the formation of hemoglobin adducts in the rats(Sprague-Dawley) administered benzidine(BZ). The experimental rats were divided into control, EtOH, and P8 groups. Rats were pretreated with EtOH or PB 24 hours before the oral administration of BZ. Blood sampling was taken before the administration of the chemicals and 0.5, 3, 6, 9, 12, 24, 48, 72, 96, and 144 hours after the administration of the BZ in 5 rats each. The blood was separated into hemoglobin and plasma immediately after taking the blood samples, and the adducts were undergone basic hydrolysis to convert them into aromatic amines. Hydrolyzed BZ, monoacetylbenzidine (MABZ), and 4-aminobiphenyl(4ABP) were separated by reversed-phase liquid chromatography without derivatization, and quantitative analyses of them were performed by a highperformance liquid chromatograph equipped with electrochemical detector. The quantitative amount of the metabolites was expressed by hemoglobin binding index(HBI), BZ-, MABZ-, and 4ABP-HBI of EtOH and PB groups were increased more than those of control group. These results are attributable to the fact that EtOH and PB induced N-hydroxylation related to the hemoglobin adduct formation. The ratio of N-acetylation (viz, MABZ-HBI/BZ-HBI) showed no significant difference between EtOH group and control group. It means that EtOH increased N-hydroxylation and N-acetylation in a similar degree. The N-acetylation ratio of PB group was relatively lower than control group because the PB increased N-hydroxylation induction. The N-acetylation ratios of all groups were higher than 1 during the entire experimental period. This result suggests that the effects of EtOH or PB need to be considered in the biochemical monitoring for the assessment of intermittent exposure of benzidine.

• Asian-Australasian Journal of Animal Sciences
• /
• v.26 no.12
• /
• pp.1680-1688
• /
• 2013

Many different approaches have been developed to improve the efficiency of animal cloning by somatic cell nuclear transfer (SCNT), one of which is to modify histone acetylation levels using histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA). In the present study, we examined the effect of TSA on in vitro development of porcine embryos derived from SCNT. We found that TSA treatment (50 nM) for 24 h following oocyte activation improved blastocyst formation rates (to 22.0%) compared with 8.9% in the non-treatment group and total cell number of the blastocysts for determining embryo quality also increased significantly ($88.9{\rightarrow}114.4$). Changes in histone acetylation levels as a result of TSA treatment were examined using indirect immunofluorescence and confocal microscopy scanning. Results showed that the histone acetylation level in TSA-treated embryos was higher than that in controls at both acetylated histone H3 lysine 9 (AcH3K9) and acetylated histone H4 lysine 12 (AcH4K12). Next, we compared the expression patterns of seven genes (OCT4, ID1; the pluripotent genes, H19, NNAT, PEG1; the imprinting genes, cytokeratin 8 and 18; the trophoblast marker genes). The SCNT blastocysts both with and without TSA treatment showed lower levels of OCT4, ID1, cytokeratin 8 and 18 than those of the in vivo blastocysts. In the case of the imprinting genes H19 and NNAT, except PEG1, the SCNT blastocysts both with and without TSA treatment showed higher levels than those of the in vivo blastocysts. Although the gene expression patterns between cloned blastocysts and their in vivo counterparts were different regardless of TSA treatment, it appears that several genes in NT blastocysts after TSA treatment showed a slight tendency toward expression patterns of in vivo blastocysts. Our results suggest that TSA treatment may improve preimplantation porcine embryo development following SCNT.