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Sample records for acetylation

  1. Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Weinert, Brian Tate; Iesmantavicius, Vytautas; Moustafa, Tarek;

    2014-01-01

    Lysine acetylation is a frequently occurring posttranslational modification; however, little is known about the origin and regulation of most sites. Here we used quantitative mass spectrometry to analyze acetylation dynamics and stoichiometry in Saccharomyces cerevisiae. We found that acetylation...

  2. Regulation of intermediary metabolism by protein acetylation

    OpenAIRE

    Guan, Kun-Liang; Xiong, Yue

    2010-01-01

    Extensive studies during the past four decades have identified important roles for lysine acetylation in the regulation of nuclear transcription. Recent proteomic analyses on protein acetylation uncovered a large number of acetylated proteins in the cytoplasm and mitochondria, including most enzymes involved in intermediate metabolism. Acetylation regulates metabolic enzymes by multiple mechanisms, including via enzymatic activation or inhibition, and by influencing protein stability. Convers...

  3. Fatal Intoxication with Acetyl Fentanyl.

    Science.gov (United States)

    Cunningham, Susan M; Haikal, Nabila A; Kraner, James C

    2016-01-01

    Among the new psychoactive substances encountered in forensic investigations is the opioid, acetyl fentanyl. The death of a 28-year-old man from recreational use of this compound is reported. The decedent was found in the bathroom of his residence with a tourniquet secured around his arm and a syringe nearby. Postmortem examination findings included marked pulmonary and cerebral edema and needle track marks. Toxicological analysis revealed acetyl fentanyl in subclavian blood, liver, vitreous fluid, and urine at concentrations of 235 ng/mL, 2400 ng/g, 131 ng/mL, and 234 ng/mL, respectively. Acetyl fentanyl was also detected in the accompanying syringe. Death was attributed to recreational acetyl fentanyl abuse, likely through intravenous administration. The blood acetyl fentanyl concentration is considerably higher than typically found in fatal fentanyl intoxications. Analysis of this case underscores the need for consideration of a wide range of compounds with potential opioid-agonist activity when investigating apparent recreational drug-related deaths. PMID:26389815

  4. Protein Acetylation in Archaea, Bacteria, and Eukaryotes

    Directory of Open Access Journals (Sweden)

    Jörg Soppa

    2010-01-01

    Full Text Available Proteins can be acetylated at the alpha-amino group of the N-terminal amino acid (methionine or the penultimate amino acid after methionine removal or at the epsilon-amino group of internal lysines. In eukaryotes the majority of proteins are N-terminally acetylated, while this is extremely rare in bacteria. A variety of studies about N-terminal acetylation in archaea have been reported recently, and it was revealed that a considerable fraction of proteins is N-terminally acetylated in haloarchaea and Sulfolobus, while this does not seem to apply for methanogenic archaea. Many eukaryotic proteins are modified by differential internal acetylation, which is important for a variety of processes. Until very recently, only two bacterial proteins were known to be acetylation targets, but now 125 acetylation sites are known for E. coli. Knowledge about internal acetylation in archaea is extremely limited; only two target proteins are known, only one of which—Alba—was used to study differential acetylation. However, indications accumulate that the degree of internal acetylation of archaeal proteins might be underestimated, and differential acetylation has been shown to be essential for the viability of haloarchaea. Focused proteomic approaches are needed to get an overview of the extent of internal protein acetylation in archaea.

  5. Acetyl-Phosphate Is a Critical Determinant of Lysine Acetylation in E. coli

    DEFF Research Database (Denmark)

    Weinert, Brian T; Iesmantavicius, Vytautas; Wagner, Sebastian A;

    2013-01-01

    Lysine acetylation is a frequently occurring posttranslational modification in bacteria; however, little is known about its origin and regulation. Using the model bacterium Escherichia coli (E. coli), we found that most acetylation occurred at a low level and accumulated in growth-arrested cells in...... acetylate lysine residues in vitro and that AcP levels are correlated with acetylation levels in vivo, suggesting that AcP may acetylate proteins nonenzymatically in cells. These results uncover a critical role for AcP in bacterial acetylation and indicate that most acetylation in E. coli occurs at a low...

  6. Swelling of acetylated wood in organic liquids

    CERN Document Server

    Obataya, E; Obataya, Eiichi; Gril, Joseph

    2005-01-01

    To investigate the affinity of acetylated wood for organic liquids, Yezo spruce wood specimens were acetylated with acetic anhydride, and their swelling in various liquids were compared to those of untreated specimens. The acetylated wood was rapidly and remarkably swollen in aprotic organic liquids such as benzene and toluene in which the untreated wood was swollen only slightly and/or very slowly. On the other hand, the swelling of wood in water, ethylene glycol and alcohols remained unchanged or decreased by the acetylation. Consequently the maximum volume of wood swollen in organic liquids was always larger than that in water. The effect of acetylation on the maximum swollen volume of wood was greater in liquids having smaller solubility parameters. The easier penetration of aprotic organic liquids into the acetylated wood was considered to be due to the scission of hydrogen bonds among the amorphous wood constituents by the substitution of hydroxyl groups with hydrophobic acetyl groups.

  7. Flow properties of acetylated chickpea protein dispersions.

    Science.gov (United States)

    Liu, Li H; Hung, Tran V

    2010-06-01

    Chickpea protein concentrate was acetylated with acetic anhydride at 5 levels. Acetylated chickpea protein (ACP) dispersions at 3 levels (6%, 45%, and 49%) were chosen for this flow property study. Effects of protein concentration, temperature, concentrations of salt addition and particularly, degree of acetylation on these properties were examined. Compared with native chickpea proteins, the ACP dispersions exhibited a strong shear thinning behavior. Within measured temperature range (15 to 55 degrees C), the apparent viscosities of native chickpea protein dispersions were temperature independent; those of ACP dispersions were thermally affected. The flow index (n), consistency coefficient (m), apparent yield stress, and apparent viscosities of ACP dispersions increased progressively up to 45% acetylation but decreased at 49% acetylation level. Conformational studies by gel filtration suggested that chickpea proteins were associated or polymerized at up to 45% acetylation but the associated subunits gradually dissociated to smaller units at higher levels (49%) of acetylation.

  8. Histone Acetylation in Drug Addiction

    OpenAIRE

    Renthal, William; Nestler, Eric J.

    2009-01-01

    Regulation of chromatin structure through post-translational modifications of histones (e.g. acetylation) has emerged as an important mechanism to translate a variety of environmental stimuli, including drugs of abuse, into specific changes in gene expression. Since alterations in gene expression are thought to contribute to the development and maintenance of the addicted state, recent efforts are aimed at identifying how drugs of abuse alter chromatin structure and the enzymes which regulate...

  9. A Method to determine lysine acetylation stoichiometries

    Energy Technology Data Exchange (ETDEWEB)

    Nakayasu, Ernesto S.; Wu, Si; Sydor, Michael A.; Shukla, Anil K.; Weitz, Karl K.; Moore, Ronald J.; Hixson, Kim K.; Kim, Jong Seo; Petyuk, Vladislav A.; Monroe, Matthew E.; Pasa-Tolic, Ljiljana; Qian, Weijun; Smith, Richard D.; Adkins, Joshua N.; Ansong, Charles

    2014-07-21

    A major bottleneck to fully understanding the functional aspects of lysine acetylation is the lack of stoichiometry information. Here we describe a mass spectrometry method using a combination of isotope labeling and detection of a diagnostic fragment ion to determine the stoichiometry of lysine acetylation on proteins globally. Using this technique, we determined the modification occupancy on hundreds of acetylated peptides from cell lysates and cross-validated the measurements via immunoblotting.

  10. Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions

    DEFF Research Database (Denmark)

    Weinert, Brian T; Moustafa, Tarek; Iesmantavicius, Vytautas;

    2015-01-01

    Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or...... suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of...... fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation...

  11. Acetylation of Chinese bamboo flour and thermoplasticity

    Institute of Scientific and Technical Information of China (English)

    LI Xue-fang; CHEN Qin-hui; LIN Jin-huo; ZHUO Dong-xian; WU Xiu-ling

    2008-01-01

    Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the trichloroacetic acid amount 6.0 g per 1.5-g bamboo flour, ultrasosonication duration 40 min and the reaction time 1 h at 65℃. The composition, microstructure and thermal behavior of acetylated bamboo flour were preliminarily characterized by FT-IR, DSC and SEM etc. The acetylated bamboo flour can be molded into sheets at 130℃ and 10 MPa, indicating the modified bamboo flour possesses thermalplastic performance.

  12. Acetylation of woody lignocellulose: significance and regulation

    Directory of Open Access Journals (Sweden)

    Prashant Mohan-Anupama Pawar

    2013-05-01

    Full Text Available Non-cellulosic cell wall polysaccharides constitute approximately one quarter of usable biomass for human exploitation. In contrast to cellulose, these components are usually substituted by O-acetyl groups, which affect their properties and interactions with other polymers, thus affecting their solubility and extractability. However, details of these interactions are still largely obscure. Moreover, polysaccharide hydrolysis to constituent monosaccharides, is hampered by the presence of O-acetyl groups, necessitating either enzymatic (esterase or chemical de-acetylation, increasing the costs and chemical consumption. Reduction of polysaccharide acetyl content in planta is a way to modify lignocellulose towards improved saccharification. In this review we: 1 summarize literature on lignocellulose acetylation in different tree species, 2 present data and current hypotheses concerning the role of O-acetylation in determining woody lignocellulose properties, 3 describe plant proteins involved in lignocellulose O-acetylation, 4 give examples of microbial enzymes capable to de-acetylate lignocellulose, and 5 discuss prospects for exploiting these enzymes in planta to modify xylan acetylation.

  13. Acetylation regulates Jun protein turnover in Drosophila.

    Science.gov (United States)

    Zhang, Daoyong; Suganuma, Tamaki; Workman, Jerry L

    2013-11-01

    C-Jun is a major transcription factor belonging to the activating protein 1 (AP-1) family. Phosphorylation has been shown to be critical for c-Jun activation and stability. Here, we report that Jra, the Drosophila Jun protein, is acetylated in vivo. We demonstrate that the acetylation of Jra leads to its rapid degradation in response to osmotic stress. Intriguingly, we also found that Jra phosphorylation antagonized its acetylation, indicating the opposite roles of acetylation and phosphorylation in Jra degradation process under osmotic stress. Our results provide new insights into how c-Jun proteins are precisely regulated by the interplay of different posttranslational modifications.

  14. Acetylation-Mediated Suppression of Transcription-Independent Memory: Bidirectional Modulation of Memory by Acetylation

    OpenAIRE

    Katja Merschbaecher; Jakob Haettig; Uli Mueller

    2012-01-01

    Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs), and the antagonistic histone deacetylases (HDACs) play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM). While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact...

  15. Proteomic profiling of lysine acetylation in Pseudomonas aeruginosa reveals the diversity of acetylated proteins.

    Science.gov (United States)

    Ouidir, Tassadit; Cosette, Pascal; Jouenne, Thierry; Hardouin, Julie

    2015-07-01

    Protein lysine acetylation is a reversible and highly regulated post-translational modification with the well demonstrated physiological relevance in eukaryotes. Recently, its important role in the regulation of metabolic processes in bacteria was highlighted. Here, we reported the lysine acetylproteome of Pseudomonas aeruginosa using a proteomic approach. We identified 430 unique peptides corresponding to 320 acetylated proteins. In addition to the proteins involved in various metabolic pathways, several enzymes contributing to the lipopolysaccharides biosynthesis were characterized as acetylated. This data set illustrated the abundance and the diversity of acetylated lysine proteins in P. aeruginosa and opens opportunities to explore the role of the acetylation in the bacterial physiology. PMID:25900529

  16. Investigation of acetyl migrations in furanosides

    Directory of Open Access Journals (Sweden)

    Migaud ME

    2006-07-01

    Full Text Available Abstract Standard reaction conditions for the desilylation of acetylated furanoside (riboside, arabinoside and xyloside derivatives facilitate acyl migration. Conditions which favour intramolecular and intermolecular mechanisms have been identified with intermolecular transesterifications taking place under mild basic conditions when intramolecular orthoester formations are disfavoured. In acetyl ribosides, acyl migration could be prevented when desilylation was catalysed by cerium ammonium nitrate.

  17. The Acetylation of Starch by Reactive Extrusion

    NARCIS (Netherlands)

    Graaf, Robbert A. de; Broekroelofs, Annet; Janssen, Léon P.B.M.

    1998-01-01

    Potato starch has been acetylated in a counter rotating twin screw extruder using vinylacetate and sodium hydroxide. The desired starch acetylation reaction is accompanied by an undesired parallel base catalysed hydrolysis reaction of vinylacetate and a consecutive hydrolysis reaction of the acetyla

  18. Histone Acetylation in Fungal Pathogens of Plants

    Directory of Open Access Journals (Sweden)

    Junhyun Jeon

    2014-03-01

    Full Text Available Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed.

  19. Acetylation-mediated suppression of transcription-independent memory: bidirectional modulation of memory by acetylation.

    Directory of Open Access Journals (Sweden)

    Katja Merschbaecher

    Full Text Available Learning induced changes in protein acetylation, mediated by histone acetyl transferases (HATs, and the antagonistic histone deacetylases (HDACs play a critical role in memory formation. The status of histone acetylation affects the interaction between the transcription-complex and DNA and thus regulates transcription-dependent processes required for long-term memory (LTM. While the majority of studies report on the role of elevated acetylation in memory facilitation, we address the impact of both, increased and decreased acetylation on formation of appetitive olfactory memory in honeybees. We show that learning-induced changes in the acetylation of histone H3 at aminoacid-positions H3K9 and H3K18 exhibit distinct and different dynamics depending on the training strength. A strong training that induces LTM leads to an immediate increase in acetylation at H3K18 that stays elevated for hours. A weak training, not sufficient to trigger LTM, causes an initial increase in acetylation at H3K18, followed by a strong reduction in acetylation at H3K18 below the control group level. Acetylation at position H3K9 is not affected by associative conditioning, indicating specific learning-induced actions on the acetylation machinery. Elevating acetylation levels by blocking HDACs after conditioning leads to an improved memory. While memory after strong training is enhanced for at least 2 days, the enhancement after weak training is restricted to 1 day. Reducing acetylation levels by blocking HAT activity after strong training leads to a suppression of transcription-dependent LTM. The memory suppression is also observed in case of weak training, which does not require transcription processes. Thus, our findings demonstrate that acetylation-mediated processes act as bidirectional regulators of memory formation that facilitate or suppress memory independent of its transcription-requirement.

  20. Efficient acetylation of primary amines and amino acids in environmentally benign brine solution using acetyl chloride

    Indian Academy of Sciences (India)

    Kaushik Basu; Suchandra Chakraborty; Achintya Kumar Sarkar; Chandan Saha

    2013-05-01

    Acetyl chloride is one of the most commonly available and cheap acylating agent but its high reactivity and concomitant instability in water precludes its use to carry out acetylation in aqueous medium. The present methodology illustrates the efficient acetylation of primary amines and amino acids in brine solution by means of acetyl chloride under weakly basic condition in the presence of sodium acetate and/or triethyl amine followed by trituration with aqueous saturated bicarbonate solution. This effort represents the first efficient use of this most reactive but cheap acetylating agent to acetylate amines in excellent yields in aqueous medium. This is a potentially useful green chemical transformation where reaction takes place in environment-friendly brine solution leading to easy work-up and isolation of the amide derivatives. Mechanistic rationale of this methodology is also important.

  1. Levels of histone acetylation in thyroid tumors.

    Science.gov (United States)

    Puppin, Cinzia; Passon, Nadia; Lavarone, Elisa; Di Loreto, Carla; Frasca, Francesco; Vella, Veronica; Vigneri, Riccardo; Damante, Giuseppe

    2011-08-12

    Histone acetylation is a major mechanism to regulate gene transcription. This post-translational modification is modified in cancer cells. In various tumor types the levels of acetylation at several histone residues are associated to clinical aggressiveness. By using immunohistochemistry we show that acetylated levels of lysines at positions 9-14 of H3 histone (H3K9-K14ac) are significantly higher in follicular adenomas (FA), papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and undifferentiated carcinomas (UC) than in normal tissues (NT). Similar data have been obtained when acetylated levels of lysine 18 of H3 histone (H3K18ac) were evaluated. In this case, however, no difference was observed between NT and UC. When acetylated levels of lysine 12 of H4 histone (H4K12ac) were evaluated, only FA showed significantly higher levels in comparison with NT. These data indicate that modification histone acetylation is an early event along thyroid tumor progression and that H3K18 acetylation is switched off in the transition between differentiated and undifferentiated thyroid tumors. By using rat thyroid cell lines that are stably transfected with doxycyclin-inducible oncogenes, we show that the oncoproteins RET-PTC, RAS and BRAF increase levels of H3K9-K14ac and H3K18ac. In the non-tumorigenic rat thyroid cell line FRTL-5, TSH increases levels of H3K18ac. However, this hormone decreases levels of H3K9-K14ac and H4K12ac. In conclusion, our data indicate that neoplastic transformation and hormonal stimulation can modify levels of histone acetylation in thyroid cells. PMID:21763277

  2. Acetylation Reader Proteins: Linking Acetylation Signaling to Genome Maintenance and Cancer.

    Science.gov (United States)

    Gong, Fade; Chiu, Li-Ya; Miller, Kyle M

    2016-09-01

    Chromatin-based DNA damage response (DDR) pathways are fundamental for preventing genome and epigenome instability, which are prevalent in cancer. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) catalyze the addition and removal of acetyl groups on lysine residues, a post-translational modification important for the DDR. Acetylation can alter chromatin structure as well as function by providing binding signals for reader proteins containing acetyl-lysine recognition domains, including the bromodomain (BRD). Acetylation dynamics occur upon DNA damage in part to regulate chromatin and BRD protein interactions that mediate key DDR activities. In cancer, DDR and acetylation pathways are often mutated or abnormally expressed. DNA damaging agents and drugs targeting epigenetic regulators, including HATs, HDACs, and BRD proteins, are used or are being developed to treat cancer. Here, we discuss how histone acetylation pathways, with a focus on acetylation reader proteins, promote genome stability and the DDR. We analyze how acetylation signaling impacts the DDR in the context of cancer and its treatments. Understanding the relationship between epigenetic regulators, the DDR, and chromatin is integral for obtaining a mechanistic understanding of genome and epigenome maintenance pathways, information that can be leveraged for targeting acetylation signaling, and/or the DDR to treat diseases, including cancer.

  3. p53 Acetylation: Regulation and Consequences

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Sara M. [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Quelle, Dawn E., E-mail: dawn-quelle@uiowa.edu [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States)

    2014-12-23

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  4. Trichoderma reesei CE16 acetyl esterase and its role in enzymatic degradation of acetylated hemicellulose

    DEFF Research Database (Denmark)

    Biely, Peter; Cziszarava, Maria; Agger, Jane W.;

    2014-01-01

    Results The combined action of GH10 xylanase and acetylxylan esterases (AcXEs) leads to formation of neutral and acidic xylooligosaccharides with a few resistant acetyl groups mainly at their non-reducing ends. We show here that these acetyl groups serve as targets for TrCE16 AcE. The most promin...

  5. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2

    DEFF Research Database (Denmark)

    Schwer, Bjoern; Bunkenborg, Jakob; Verdin, Regis O;

    2006-01-01

    by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. This report identifies the first acetylated substrate protein of SIRT3. Our findings show that a mammalian sirtuin directly controls the activity of a metabolic enzyme by means of reversible lysine acetylation. Because the activity......We report that human acetyl-CoA synthetase 2 (AceCS2) is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo. Deacetylation of AceCS2...

  6. Proteomic analysis of acetylation in thermophilic Geobacillus kaustophilus.

    Science.gov (United States)

    Lee, Dong-Woo; Kim, Dooil; Lee, Yong-Jik; Kim, Jung-Ae; Choi, Ji Young; Kang, Sunghyun; Pan, Jae-Gu

    2013-08-01

    Recent analysis of prokaryotic N(ε)-lysine-acetylated proteins highlights the posttranslational regulation of a broad spectrum of cellular proteins. However, the exact role of acetylation remains unclear due to a lack of acetylated proteome data in prokaryotes. Here, we present the N(ε)-lysine-acetylated proteome of gram-positive thermophilic Geobacillus kaustophilus. Affinity enrichment using acetyl-lysine-specific antibodies followed by LC-MS/MS analysis revealed 253 acetylated peptides representing 114 proteins. These acetylated proteins include not only common orthologs from mesophilic Bacillus counterparts, but also unique G. kaustophilus proteins, indicating that lysine acetylation is pronounced in thermophilic bacteria. These data complement current knowledge of the bacterial acetylproteome and provide an expanded platform for better understanding of the function of acetylation in cellular metabolism.

  7. 21 CFR 172.828 - Acetylated monoglycerides.

    Science.gov (United States)

    2010-04-01

    ... molecular distillation or by steam stripping; or (2) The direct acetylation of edible monoglycerides with acetic anhydride without the use of catalyst or molecular distillation, and with the removal by vacuum distillation, if necessary, of the acetic acid, acetic anhydride, and triacetin. (b) The food additive has...

  8. Acetylated flavonol triglycosides from Ammi majus L.

    Science.gov (United States)

    Singab, A N

    1998-12-01

    Two new acetylated flavonol triglycosides: kaempferol and isorhamnetin 3-O-[2"-(4"'-acetylrhamnosyl)-6"-glucosyl] glucosides, were isolated and identified from the aerial parts of Ammi majus L. In addition, three known flavonol glycosides namely; isorhamnetin-3-O-rutinoside, kaempferol-3-O-glucoside and isorhamnetin-3-O-glucoside were detected.

  9. Oxidative Debenzylation and Acetylation of Hexabenzylhexaazaisowutzitane

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The oxidative reactivity of hexabenzylhexaazaisowutzitane(HBIW)under different conditions was studied. It was found that the N-benzyl groups were found to form benzoyl group after oxidation. They might also be first debenzylated and then acetylated by potassium permanganate in acetic anhydride/DMF.

  10. Two New Acetyl Cimicifugosides from the Rhizomes of Cimicifuga Racemosa

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Two new acetyl cimicifugosides were isolated from the rhizomes of Cimicifuga racemosa. Their structures were elucidated as 2'-O-acetyl cimicifugoside H-1 1 and 3'-O-acetyl cimicifugoside H-1 2 by the spectroscopic evidence and chemical methods.

  11. Acetylation Is Indispensable for p53 Activation

    OpenAIRE

    Tang, Yi; Zhao, Wenhui; Chen, Yue; Zhao, Yingming; Gu, Wei

    2008-01-01

    The activation of the tumor suppressor p53 facilitates the cellular response to genotoxic stress; however, the p53 response can only be executed if its interaction with its inhibitor Mdm2 is abolished. There have been conflicting reports on the question of whether p53 posttranslational modifications, such as phosphorylation or acetylation, are essential or only play a subtle, fine-tuning role in the p53 response. Thus, it remains unclear whether p53 modification is absolutely required for its...

  12. p53 Acetylation: Regulation and Consequences

    OpenAIRE

    Reed, Sara M.; Quelle, Dawn E.

    2014-01-01

    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo ev...

  13. Fragrance material review on acetyl cedrene.

    Science.gov (United States)

    Scognamiglio, J; Letizia, C S; Politano, V T; Api, A M

    2013-12-01

    A toxicologic and dermatologic review of acetyl cedrene when used as a fragrance ingredient is presented. Acetyl cedrene is a member of the fragrance structural group Alkyl Cyclic Ketones. The generic formula for this group can be represented as (R1)(R2)CO. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for acetyl cedrene were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, and genotoxicity data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (2013) (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients. Submitted with this manuscript.) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. PMID:23907023

  14. Acetylation phenotype variation in pediatric patients with atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Rafi A Majeed Al-Razzuqi

    2011-01-01

    Full Text Available Background: Few studies have been done on the relation between acetylator status and allergic diseases. Aim: To determine any possible association between acetylating phenotype in pediatric patients with atopic dermatitis (AD and the disease prognosis. Patients and Methods: Thirty-six pediatric patients and forty two healthy children as a control group were participated in the study. All participants received a single oral dose of dapsone of 1.54 mg/kg body weight, after an overnight fast. Using high performance liquid chromatography (HPLC, plasma concentrations of dapsone and its metabolite (monoacetyldapsone were estimated to phenotype the participants as slow and rapid acetylators according to their acetylation ratio (ratio of monoacetyldapsone to dapsone. Results: 72.2% of pediatric patients with AD showed slow acetylating status as compared to 69.4% of control individuals. Also, 73% of AD patients with slow acetylating phenotype had familial history of allergy. The severity of AD occurred only in slow acetylator patients. The eczematous lesions in slow acetylators presented mainly in the limbs, while in rapid acetylators, they were found mostly in face and neck. Conclusion: This study shows an association between the N-acetylation phenotype variation and clinical aspects of AD.

  15. Determination of amphetamine by HPLC after acetylation.

    Science.gov (United States)

    Veress, T

    2000-01-01

    An analytical procedure has been developed for the HPLC determination of amphetamine by off-line pre-column derivatization. The proposed procedure consists of sample preparation by acetylation of amphetamine with acetic anhydride and a subsequent reversed-phase HPLC separation on an octadecyl silica stationary phase with salt-free mobile phase (tetrahydrofuran, acetonitrile, 0.1% triethylamine in water, 15:15:70 v/v) applying UV-detection. The applicability of the elaborated procedure is demonstrated with results obtained by analysis of real samples seized in the Hungarian black market. PMID:10641931

  16. Getting a Knack for NAC: N-Acetyl-Cysteine

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2011-01-01

    N-acetyl-cysteine, N-acetylcysteine, N-acetyl cysteine, and N-acetyl-L-cysteine are all designations for the same compound, which is abbreviated as NAC. NAC is a precursor to the amino acid cysteine, which ultimately plays two key metabolic roles. Through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. Through its role as a modulator of the glutamatergic system, cysteine influences the reward-reinforcement pathway....

  17. Obesity, cancer, and acetyl-CoA metabolism

    OpenAIRE

    Lee, Joyce V.; Shah, Supriya A.; Wellen, Kathryn E.

    2013-01-01

    As rates of obesity soar in the Unites States and around the world, cancer attributed to obesity has emerged as major threat to public health. The link between obesity and cancer can be attributed in part to the state of chronic inflammation that develops in obesity. Acetyl-CoA production and protein acetylation patterns are highly sensitive to metabolic state and are significantly altered in obesity. In this article, we explore the potential role of nutrient-sensitive lysine acetylation in r...

  18. Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy

    OpenAIRE

    Min, Sang-Won; Cho, Seo-Hyun; Zhou, Yungui; Schroeder, Sebastian; Haroutunian, Vahram; Seeley, William W.; Huang, Eric J.; Shen, Yong; Masliah, Eliezer; Mukherjee, Chandrani; Meyers, David; Cole, Philip A.; Ott, Melanie; Gan, Li

    2010-01-01

    Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). Using two antibodies specific for acetylated ta...

  19. Lipase-catalyzed synthesis of acetylated EGCG and antioxidant properties of the acetylated derivatives

    Science.gov (United States)

    (-)-Epigallocatechin-3-O-gallate (EGCG) acetylated derivatives were prepared by lipase catalyzed acylation of EGCG with vinyl acetate to improve its lipophilicity and expand its application in lipophilic media. The immobilized lipase, Lipozyme RM IM, was found to be the optimum catalyst. The optimiz...

  20. Protein lysine acetylation in bacteria: Current state of the art.

    Science.gov (United States)

    Ouidir, Tassadit; Kentache, Takfarinas; Hardouin, Julie

    2016-01-01

    Post-translational modifications of proteins are key events in cellular metabolism and physiology regulation. Lysine acetylation is one of the best studied protein modifications in eukaryotes, but, until recently, ignored in bacteria. However, proteomic advances have highlighted the diversity of bacterial lysine-acetylated proteins. The current data support the implication of lysine acetylation in various metabolic pathways, adaptation and virulence. In this review, we present a broad overview of the current knowledge of lysine acetylation in bacteria. We emphasize particularly the significant contribution of proteomics in this field. PMID:26390373

  1. N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes.

    Science.gov (United States)

    Prokesch, A; Pelzmann, H J; Pessentheiner, A R; Huber, K; Madreiter-Sokolowski, C T; Drougard, A; Schittmayer, M; Kolb, D; Magnes, C; Trausinger, G; Graier, W F; Birner-Gruenberger, R; Pospisilik, J A; Bogner-Strauss, J G

    2016-04-05

    Histone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA. Here, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. N-acetylaspartate (NAA) is a highly abundant brain metabolite catabolized by aspartoacylase yielding aspartate and acetate. The latter can be further used for acetyl-CoA production. Prior to this work, the presence of NAA has not been described in adipocytes. Here, we show that accumulation of NAA decreases the brown adipocyte phenotype. We increased intracellular NAA concentrations in brown adipocytes via media supplementation or knock-down of aspartoacylase and measured reduced lipolysis, thermogenic gene expression, and oxygen consumption. Combinations of approaches to increase intracellular NAA levels showed additive effects on lipolysis and gene repression, nearly abolishing the expression of Ucp1, Cidea, Prdm16, and Ppara. Transcriptome analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac and H3K9ac) in promoters/enhancers of brown marker genes showed reduced acetylation status. Taken together, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect the NAA pathway to the epigenomic regulation of gene expression, modulating the phenotype of brown adipocytes.

  2. The kinetics of the acetylation of gelatinised potato starch

    NARCIS (Netherlands)

    de Graaf, R.A.; Broekroelofs, G.A.; Janssen, L.P.B.M.; Beenackers, A.A C M

    1995-01-01

    The reaction rates, in the base-catalysed acetylation of gelatinised aqueous starch (4 wt%), by vinylacetate (ViAc), were investigated in a semibatch reactor at temperatures ranging from 20 to 50 degrees C. The desired starch acetylation reaction is accompanied by an undesired parallel base-catalyse

  3. Regulation of autophagy by cytosolic acetyl-coenzyme A

    DEFF Research Database (Denmark)

    Mariño, Guillermo; Pietrocola, Federico; Eisenberg, Tobias;

    2014-01-01

    Acetyl-coenzyme A (AcCoA) is a major integrator of the nutritional status at the crossroads of fat, sugar, and protein catabolism. Here we show that nutrient starvation causes rapid depletion of AcCoA. AcCoA depletion entailed the commensurate reduction in the overall acetylation of cytoplasmic p...

  4. Medial temporal N-acetyl-aspartate in pediatric major depression.

    Science.gov (United States)

    MacMaster, Frank P; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S Preeya; Buhagiar, Christian; Rosenberg, David R

    2008-10-30

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD case-control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in the left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  5. Medial temporal N-acetyl aspartate in pediatric major depression

    Science.gov (United States)

    MacMaster, Frank P.; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S. Preeya; Buhagiar, Christian; Rosenberg, David R.

    2008-01-01

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD-case control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  6. 21 CFR 172.372 - N-Acetyl-L-methionine.

    Science.gov (United States)

    2010-04-01

    ... HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.372 N-Acetyl-L-methionine. The food additive N-acetyl-L... section. The minimum amount of the additive to achieve the desired effect must be used, and the...

  7. Trichostatin A induced histone acetylation causes decondensation of interphase chromatin.

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); M. Wachsmuth (Malte); M. Frank-Stöhr (Monika); M. Stöhr (Michael); C.P. Bacher (Christian); K. Rippe (Karsten)

    2004-01-01

    textabstractThe effect of trichostatin A (TSA)-induced histone acetylation on the interphase chromatin structure was visualized in vivo with a HeLa cell line stably expressing histone H2A, which was fused to enhanced yellow fluorescent protein. The globally increased histone acetylation caused a rev

  8. A facile and practical synthesis of N-acetyl enamides.

    Science.gov (United States)

    Tang, Wenjun; Capacci, Andrew; Sarvestani, Max; Wei, Xudong; Yee, Nathan K; Senanayake, Chris H

    2009-12-18

    A facile and practical method for the synthesis of N-acetyl alpha-arylenamides has been developed from corresponding ketoximes as the starting materials with ferrous acetate as the reducing reagent. This methodology offers mild reaction conditions, simple purification procedures, and high yields for a variety of N-acetyl enamides. PMID:19921804

  9. Unchanged acetylation of isoniazid by alcohol intake

    DEFF Research Database (Denmark)

    Wilcke, J T R; Døssing, M; Angelo, H R;

    2004-01-01

    no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.......SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral...... dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has...

  10. The biology of lysine acetylation integrates transcriptional programming and metabolism

    Directory of Open Access Journals (Sweden)

    Mujtaba Shiraz

    2011-03-01

    Full Text Available Abstract The biochemical landscape of lysine acetylation has expanded from a small number of proteins in the nucleus to a multitude of proteins in the cytoplasm. Since the first report confirming acetylation of the tumor suppressor protein p53 by a lysine acetyltransferase (KAT, there has been a surge in the identification of new, non-histone targets of KATs. Added to the known substrates of KATs are metabolic enzymes, cytoskeletal proteins, molecular chaperones, ribosomal proteins and nuclear import factors. Emerging studies demonstrate that no fewer than 2000 proteins in any particular cell type may undergo lysine acetylation. As described in this review, our analyses of cellular acetylated proteins using DAVID 6.7 bioinformatics resources have facilitated organization of acetylated proteins into functional clusters integral to cell signaling, the stress response, proteolysis, apoptosis, metabolism, and neuronal development. In addition, these clusters also depict association of acetylated proteins with human diseases. These findings not only support lysine acetylation as a widespread cellular phenomenon, but also impel questions to clarify the underlying molecular and cellular mechanisms governing target selectivity by KATs. Present challenges are to understand the molecular basis for the overlapping roles of KAT-containing co-activators, to differentiate between global versus dynamic acetylation marks, and to elucidate the physiological roles of acetylated proteins in biochemical pathways. In addition to discussing the cellular 'acetylome', a focus of this work is to present the widespread and dynamic nature of lysine acetylation and highlight the nexus that exists between epigenetic-directed transcriptional regulation and metabolism.

  11. Reduced Wall Acetylation Proteins Play Vital and Distinct Roles in Cell Wall O-Acetylation in Arabidopsis

    DEFF Research Database (Denmark)

    Manabe, Yuzuki; Verhertbruggen, Yves; Gille, Sascha;

    2013-01-01

    . The quadruple rwa mutant can be completely complemented with the RWA2 protein expressed under 35S promoter, indicating the functional redundancy of the RWA proteins. Nevertheless, the degree of acetylation of xylan, (gluco) mannan, and xyloglucan as well as overall cell wall acetylation is affected differently...

  12. Partially Acetylated Sugarcane Bagasse For Wicking Oil From Contaminated Wetlands

    Science.gov (United States)

    Sugarcane bagasse was partially acetylated to enhance its oil-wicking ability in saturated environments while holding moisture for hydrocarbon biodegradation. The water sorption capacity of raw bagasse was reduced fourfold after treatment, which indicated considerably increased ...

  13. Phosphorylation and Acetylation of Acyl-CoA Synthetase- I

    DEFF Research Database (Denmark)

    Frahm, Jennifer L; Li, Lei O; Grevengoed, Trisha J;

    2011-01-01

    -translational regulation. In order to investigate the post-translational modifications of ACSL1 under different physiological conditions, we overexpressed ACSL1 in hepatocytes, brown adipocytes, and 3T3-L1 differentiated adipocytes, treated these cells with different hormones, and analyzed the resulting phosphorylated...... and acetylated amino acids by mass spectrometry. We then compared these results to the post-translational modifications observed in vivo in liver and brown adipose tissue after mice were fasted or exposed to a cold environment. We identified universal N-terminal acetylation, 15 acetylated lysines, and 25......-directed mutagenesis was used to introduce mutations at three potential acetylation and phosphorylation sites believed to be important for ACSL1 function. At the ATP/AMP binding site and at a highly conserved site near the C terminus, modifications of Ser278 or Lys676, respectively, totally inhibited ACSL1 activity...

  14. Function-structure relationships of acetylated pea starches

    OpenAIRE

    J. Huang

    2006-01-01

    Cowpea, chickpea and yellow pea starches were studied and the results showed that their properties were strongly related to the chemical fine structures of the starches. Furthermore, granular starches were modified using two types of chemical acetylation reagents and then separated into different size fractions. The amount of introduced acetyl groups was found to depend on the size of the granules for the reaction with rapidly reacting reagent acetic acid anhydride, whereas the amount of intr...

  15. The growing landscape of lysine acetylation links metabolism and cell signalling

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Weinert, Brian Tate; Nishida, Yuya;

    2014-01-01

    Lysine acetylation is a conserved protein post-translational modification that links acetyl-coenzyme A metabolism and cellular signalling. Recent advances in the identification and quantification of lysine acetylation by mass spectrometry have increased our understanding of lysine acetylation, im...

  16. Oil spill sorption using raw and acetylated sugarcane bagasse

    Institute of Scientific and Technical Information of China (English)

    Reza Behnood; Bagher Anvaripour; Nematollah Jaafarzadeh; Masoome Farasati

    2016-01-01

    In the recent decades oil spills in the aquatic environments are one of the major sources of environmental pollutions, which are steadily growing with the increase in oil consumption. Adsorption is a rapid and cost effective processto minimize the environmental impacts of oil spills andcleanup these pollutants. In this work, the crude oil sorption capacity was examined with raw sugarcane bagasse and acetylated sugarcane bagasse. Results show that the acetylated bagasse was significantly more oleophilic than the raw bagasse and acetylation reaction can increase bagasse oil sorption ability by about 90%. The maximum sorption capacities of acetylated bagasse were obtained about 11.3 g and 9.1 g in dry system (crude oil sorption) and oil layer sorption, respectively. The physicochemical characteristics of the sorbents such as composition, water solubility, moisture content and density were measured according to ASTM standard methods. Also Fourier transform infrared spectroscopy (FTIR) of raw and acetylated bagasse was performed to investigate the effect of acetylation on sugarcane bagasse structure.

  17. Site-specific acetylation of ISWI by GCN5

    Directory of Open Access Journals (Sweden)

    Chioda Mariacristina

    2007-08-01

    Full Text Available Abstract Background The tight organisation of eukaryotic genomes as chromatin hinders the interaction of many DNA-binding regulators. The local accessibility of DNA is regulated by many chromatin modifying enzymes, among them the nucleosome remodelling factors. These enzymes couple the hydrolysis of ATP to disruption of histone-DNA interactions, which may lead to partial or complete disassembly of nucleosomes or their sliding on DNA. The diversity of nucleosome remodelling factors is reflected by a multitude of ATPase complexes with distinct subunit composition. Results We found further diversification of remodelling factors by posttranslational modification. The histone acetyltransferase GCN5 can acetylate the Drosophila remodelling ATPase ISWI at a single, conserved lysine, K753, in vivo and in vitro. The target sequence is strikingly similar to the N-terminus of histone H3, where the corresponding lysine, H3K14, can also be acetylated by GCN5. The acetylated form of ISWI represents a minor species presumably associated with the nucleosome remodelling factor NURF. Conclusion Acetylation of histone H3 and ISWI by GCN5 is explained by the sequence similarity between the histone and ISWI around the acetylation site. The common motif RKT/SxGx(KacxPR/K differs from the previously suggested GCN5/PCAF recognition motif GKxxP. This raises the possibility of co-regulation of a nucleosome remodelling factor and its nucleosome substrate through acetylation of related epitopes and suggests a direct crosstalk between two distinct nucleosome modification principles.

  18. Acetyl radical generation in cigarette smoke: Quantification and simulations

    Science.gov (United States)

    Hu, Na; Green, Sarah A.

    2014-10-01

    Free radicals are present in cigarette smoke and can have a negative effect on human health. However, little is known about their formation mechanisms. Acetyl radicals were quantified in tobacco smoke and mechanisms for their generation were investigated by computer simulations. Acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5-tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high-performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography-mass spectrometry (LC-MS). Simulations were performed using the Master Chemical Mechanism (MCM). A range of 10-150 nmol/cigarette of acetyl radical was measured from gas phase tobacco smoke of both commercial and research cigarettes under several different smoking conditions. More radicals were detected from the puff smoking method compared to continuous flow sampling. Approximately twice as many acetyl radicals were trapped when a glass fiber particle filter (GF/F specifications) was placed before the trapping zone. Simulations showed that NO/NO2 reacts with isoprene, initiating chain reactions to produce hydroxyl radical, which abstracts hydrogen from acetaldehyde to generate acetyl radical. These mechanisms can account for the full amount of acetyl radical detected experimentally from cigarette smoke. Similar mechanisms may generate radicals in second hand smoke.

  19. A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity

    OpenAIRE

    Kim, Dong-Hyun; Xiao, Zhen; Kwon, Sanghoon; Sun, Xiaoxiao; Ryerson, Daniel; Tkac, David; Ma, Ping; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Zhou, Edward; Xu, H. Eric; Palvimo, Jorma J; Chen, Lin-Feng; Kemper, Byron; Kemper, Jongsook Kim

    2014-01-01

    Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profilin...

  20. Histones of Chlamydomonas reinhardtii. Synthesis, acetylation, and methylation

    International Nuclear Information System (INIS)

    Histones of the green alga Chlamydomonas reinhardtii were prepared by a new method and fractionated by reversed-phase high-performance liquid chromatography. Acid-urea-Triton gel analysis and tritiated acetate labeling demonstrated high levels of steady-state acetylation for the single histone H3 protein, in contrast to low levels on histones H4 and H2B. Twenty percent of histone H3 is subject to dynamic acetylation with, on average, three acetylated lysine residues per protein molecule. Histone synthesis in light-dark-synchronized cultures was biphasic with pattern differences between two histone H1 variants, between two H2A variants, and between H2B and ubiquitinated H2B. Automated protein sequence analysis of histone H3 demonstrated a site-specific pattern of steady-state acetylation between 7 and 17% at five of the six amino-terminal lysines and of monomethylation between 5 and 81% at five of the eight amino-terminal lysines in a pattern that may limit dynamic acetylation. An algal histone H3 sequence was confirmed by protein sequencing with a since threonine as residue 28 instead of the serine(28)-alanine(29) sequence, present in all other known plant and animal H3 histones

  1. Curcumin-induced Histone Acetylation in Malignant Hematologic Cells

    Institute of Scientific and Technical Information of China (English)

    Junbin HU; Yan WANG; Yan CHEN

    2009-01-01

    This study investigated the inhibitory effects of curcumin on proliferation of hemato-logical malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacety-lation levels.The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay.The expression of acetylated histone-3 (H3) in Raji,HL60 and K562 cells,and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS.The results showed curcumin inhibited pro-liferation of Raji cells significantly in a time- and dose-dependent fashion,while exhibited low toxic-ity in PBMCs.Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested.In conclusion,curcumin inhibited proliferation of Raji cells selec-tively,enhanced the level of acetylated H3 in Raji,HL60,and K562 cells,which acted as a histone deacetylase inhibitor like TSA.Furthermore,up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.

  2. Recycling and Reuse of Ionic Liquid in Homogeneous Cellulose Acetylation

    Institute of Scientific and Technical Information of China (English)

    HUANG Kelin; WU Rui; CAO Yan; LI Huiquan; WANG Jinshu

    2013-01-01

    Molecular distillation was used to recover ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimC1) in homogeneous cellulose acetylation.The five factors that affect the separation efficiency of molecular distillation,namely,feed flow rate,distillation temperature,feed temperature,wiper rotating speed,and distillation pressure,are discussed.The optimal recovery condition was determined via orthogonal experiments using an OA9(34) design.The IL was recycled and reused 5 times in the homogeneous cellulose acetylation system under optimal conditions.The purity of recycled IL the 5th time reached 99.56%.FT-IR (Fourier transform infrared spectroscopy) and 1H NMR (nuclear magnetic resonance) spectroscopy showed that the structure of the recovered IL is not changed.This work proves that AmirnCl has excellent reusability,and that molecular distillation is an effective method for recovering IL in homogeneous cellulose acetylation.

  3. H4K44 Acetylation Facilitates Chromatin Accessibility during Meiosis

    Directory of Open Access Journals (Sweden)

    Jialei Hu

    2015-12-01

    Full Text Available Meiotic recombination hotspots are associated with histone post-translational modifications and open chromatin. However, it remains unclear how histone modifications and chromatin structure regulate meiotic recombination. Here, we identify acetylation of histone H4 at Lys44 (H4K44ac occurring on the nucleosomal lateral surface. We show that H4K44 is acetylated at pre-meiosis and meiosis and displays genome-wide enrichment at recombination hotspots in meiosis. Acetylation at H4K44 is required for normal meiotic recombination, normal levels of double-strand breaks (DSBs during meiosis, and optimal sporulation. Non-modifiable H4K44R results in increased nucleosomal occupancy around DSB hotspots. Our results indicate that H4K44ac functions to facilitate chromatin accessibility favorable for normal DSB formation and meiotic recombination.

  4. Synthesis of polyrotaxanes from acetyl-β-cyclodextrin

    Science.gov (United States)

    Ristić, I. S.; Nikolić, L.; Nikolić, V.; Ilić, D.; Budinski-Simendić, J.

    2011-12-01

    Polyrotaxanes are intermediary products in the synthesis of topological gels. They are created by inclusion complex formation of hydrophobic linear macromolecules with cyclodextrins or their derivatives. Then, pairs of cyclodextrin molecules with covalently linkage were practically forming the nodes of the semi-flexible polymer network. Such gels are called topological gels and they can absorb huge quantities of water due to the net flexibility allowing the poly(ethylene oxide) chains to slide through the cyclodextrin cavities, without being pulled out altogether. For polyrotaxane formation poly(ethylene oxide) was used like linear macromolecules. There are hydroxyl groups at poly(ethylene oxide) chains, whereby the linking of the voluminous molecules should be made. To avoid the reaction of cyclodextrin OH groups with stoppers, they should be protected by, e.g., acetylation. In this work, the acetylation of the OH groups of β-cyclodextrin was performed by acetic acid anhydride with iodine as the catalyst. The acetylation reaction was assessed by the FTIR and HPLC method. By the HPLC analysis was found that the acetylation was completed in 20 minutes. Inserting of poly(ethylene oxide) with 4000 g/mol molecule mass into acetyl-β-cyclodextrin with 2:1 poly(ethylene oxide) monomer unit to acetyl-β-cyclodextrin ratio was also monitored by FTIR, and it was found that the process was completed in 12 h at the temperature of 10°C. If the process is performed at temperatures above 10°C, or for periods longer than 12 hours, the process of uncontrolled hydrolysis of acetate groups was initiated.

  5. Study on Reactions of 2-Acetyl-7-methylaminotropone with Pyridinecarboxyaldehydes

    Institute of Scientific and Technical Information of China (English)

    GAO Wen-Tao; ZHENG Zhuo

    2003-01-01

    @@ Cinnamoyl group is a versatile constituent because of bearing active carbonyl group and α, β-unsaturated car bon-carbon double bond. A wide variety of heterocycle-fused troponoid compounds have been derived from cinnamoyl-substituted tropones. For examples, the 3-(4-aryl-3-cyano-2- methoxypyridin-6-yl)tropones were synthesized by the reactions of 2-acetyl-7-methylaminotropone with malononitrile via michael addition and cyclization. [1] There have been some reports about the synthesis of 2-cinnamoyl-7-methylaminotropone, [2,3] herein we further report the synthesis of this kind of compounds by the reactions of 2-acetyl-7-methylaminotropone with pyridinecarboxyaldehydes.

  6. New lysine-acetylated proteins screened by immunoaffinity and liquid chromatography-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The lack of selective extraction specific for lysine-acetylated proteins has been a major problem in the field of acetylation biology,though acetylation plays a key role in many biological processes.In this paper,we report for the first time the proteomic screening of lysine-acetylated proteins from a mouse liver tissue,by a new approach of immunoaffinity purification of lysine-acetylated peptides combined with nano-HPLC/MS/MS analysis.We have found 20 lysine-acetylated proteins with 21 lysine-acetylated sites,among which 12 lysine-acetylated proteins and 16 lysine-acetylated sites have never been reported before.Notably,three acetyltransferases harboring in mitochondrion are newly discovered acetyltransferases responsible for the acetylation of nonhistone proteins.We have explored the significant patterns of residue preference by the hierarchical clustering analysis of amino acid residues surrounding acetylation sites,which could be helpful to the prediction of new sites of lysine acetylation.Our findings provide more candidates for studying the important roles played by acetylation in diverse cellular pathways and related human diseases.

  7. SCANDIUM TRIFLATE CATALYZED ACETYLATION OF STARCH UNDER MILD CONDITIONS

    Science.gov (United States)

    Scandium (III) trifluoromethan sulfonate (Sc(OTf)3) was investigated as a catalyst for the acetylation of starch in order to determine the potential for preparing new types of starch esters under mild conditions. At room temperature, dry granular corn starch reacts with acetic anhydride in the pres...

  8. The potential role of wood acetylation in climate change mitigation

    NARCIS (Netherlands)

    Van der Lugt, P.; Vogtländer, J.G.; Alexander, J.; Bongers, F.; Stebbins, H.

    2014-01-01

    In a carbon footprint assessment, the greenhouse gas emissions during the life cycle of a material can be measured, and compared to alternative products in terms of kg CO2 equivalent. If applied correctly, wood acetylation opens up a range of new innovative applications in which high performance yet

  9. Surface effects in the acetylation of granular potato starch

    NARCIS (Netherlands)

    Steeneken, P.A.M.; Woortman, A.J.J.

    2008-01-01

    The occurrence of surface effects in the acetylation of granular potato starch with acetic anhydride to degrees of substitution 0.04-0.2 was studied by two different approaches. The first approach involved the fractionation of granular starch acetates into five different size classes and analysis of

  10. Predicting post-translational lysine acetylation using support vector machines

    DEFF Research Database (Denmark)

    Gnad, Florian; Ren, Shubin; Choudhary, Chunaram;

    2010-01-01

    spectrometry to identify 3600 lysine acetylation sites on 1750 human proteins covering most of the previously annotated sites and providing the most comprehensive acetylome so far. This dataset should provide an excellent source to train support vector machines (SVMs) allowing the high accuracy in silico...

  11. Lysine Ubiquitination and Acetylation of Human Cardiac 20S Proteasomes

    Science.gov (United States)

    Lau, Edward; Choi, Howard JH; Ng, Dominic CM; Meyer, David; Fang, Caiyun; Li, Haomin; Wang, Ding; Zelaya, Ivette M; Yates, John R; Lam, Maggie PY

    2016-01-01

    Purpose Altered proteasome functions are associated with multiple cardiomyopathies. While the proteasome targets poly-ubiquitinated proteins for destruction, it itself is modifiable by ubiquitination. We aim to identify the exact ubiquitination sites on cardiac proteasomes and examine whether they are also subject to acetylations. Experimental design Assembled cardiac 20S proteasome complexes were purified from five human hearts with ischemic cardiomyopathy, then analyzed by high-resolution MS to identify ubiquitination and acetylation sites. We developed a library search strategy that may be used to complement database search in identifying PTM in different samples. Results We identified 63 ubiquitinated lysines from intact human cardiac 20S proteasomes. In parallel, 65 acetylated residues were also discovered, 39 of which shared with ubiquitination sites. Conclusion and clinical relevance This is the most comprehensive characterization of cardiac proteasome ubiquitination to-date. There are significant overlaps between the discovered ubiquitination and acetylation sites, permitting potential crosstalk in regulating proteasome functions. The information presented here will aid future therapeutic strategies aimed at regulating the functions of cardiac proteasomes. PMID:24957502

  12. Function-structure relationships of acetylated pea starches

    NARCIS (Netherlands)

    Huang, J.

    2006-01-01

    Cowpea, chickpea and yellow pea starches were studied and the results showed that their properties were strongly related to the chemical fine structures of the starches. Furthermore, granular starches were modified using two types of chemical acetylation reagents and then separated into different si

  13. Lysine Acetylation Facilitates Spontaneous DNA Dynamics in the Nucleosome.

    Science.gov (United States)

    Kim, Jongseong; Lee, Jaehyoun; Lee, Tae-Hee

    2015-12-01

    The nucleosome, comprising a histone protein core wrapped around by DNA, is the fundamental packing unit of DNA in cells. Lysine acetylation at the histone core elevates DNA accessibility in the nucleosome, the mechanism of which remains largely unknown. By employing our recently developed hybrid single molecule approach, here we report how the structural dynamics of DNA in the nucleosome is altered upon acetylation at histone H3 lysine 56 (H3K56) that is critical for elevated DNA accessibility. Our results indicate that H3K56 acetylation facilitates the structural dynamics of the DNA at the nucleosome termini that spontaneously and repeatedly open and close on a ms time scale. The results support a molecular mechanism of histone acetylation in catalyzing DNA unpacking whose efficiency is ultimately limited by the spontaneous DNA dynamics at the nucleosome temini. This study provides the first and unique experimental evidence revealing a role of protein chemical modification in directly regulating the kinetic stability of the DNA packing unit.

  14. File list: His.Prs.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Prs.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Prost...ate http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Prs.50.Pan_lysine_acetylation.AllCell.bed ...

  15. File list: His.Myo.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: His.Unc.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Unc.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Unclas...sified http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Unc.50.Pan_lysine_acetylation.AllCell.bed ...

  17. File list: His.Prs.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: His.Epd.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: His.Lng.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: His.Pan.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: His.CDV.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: His.Epd.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: His.Adp.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: His.Prs.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: His.Bld.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Blood... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.Pan_lysine_acetylation.AllCell.bed ...

  6. File list: His.Oth.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Others... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.Pan_lysine_acetylation.AllCell.bed ...

  7. File list: His.Lng.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Lung h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Lng.50.Pan_lysine_acetylation.AllCell.bed ...

  8. File list: His.ALL.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: His.Epd.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: His.Neu.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: His.Plc.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: His.PSC.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: His.Liv.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: His.Pan.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.05.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Pancr...eas http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Pan.05.Pan_lysine_acetylation.AllCell.bed ...

  15. File list: His.Brs.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Breast... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.20.Pan_lysine_acetylation.AllCell.bed ...

  16. File list: His.ALL.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.ALL.20.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation All c...ell types SRX099890 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.ALL.20.Pan_lysine_acetylation.AllCell.bed ...

  17. File list: His.Bld.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Blood ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.Pan_lysine_acetylation.AllCell.bed ...

  18. File list: His.Liv.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Liv.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Liver ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.20.Pan_lysine_acetylation.AllCell.bed ...

  19. File list: His.Emb.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Emb.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Embryo... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Emb.10.Pan_lysine_acetylation.AllCell.bed ...

  20. File list: His.Gon.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Gon.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Gonad... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Gon.50.Pan_lysine_acetylation.AllCell.bed ...

  1. File list: His.Unc.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Unc.05.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Unclas...sified http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Unc.05.Pan_lysine_acetylation.AllCell.bed ...

  2. File list: His.Utr.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Utr.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Uterus... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Utr.20.Pan_lysine_acetylation.AllCell.bed ...

  3. File list: His.ALL.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.ALL.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation All c...ell types SRX099890 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.ALL.10.Pan_lysine_acetylation.AllCell.bed ...

  4. File list: His.Bld.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Blood ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.Pan_lysine_acetylation.AllCell.bed ...

  5. File list: His.Bld.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Blood... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.10.Pan_lysine_acetylation.AllCell.bed ...

  6. File list: His.PSC.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Pluri...potent stem cell http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.PSC.50.Pan_lysine_acetylation.AllCell.bed ...

  7. File list: His.PSC.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Plurip...otent stem cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.PSC.10.Pan_lysine_acetylation.AllCell.bed ...

  8. File list: His.Adp.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Adipo...cyte http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Adp.50.Pan_lysine_acetylation.AllCell.bed ...

  9. File list: His.Prs.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Prs.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Prosta...te http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Prs.50.Pan_lysine_acetylation.AllCell.bed ...

  10. File list: His.Neu.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Neural... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.Pan_lysine_acetylation.AllCell.bed ...

  11. File list: His.CDV.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.CDV.05.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Cardi...ovascular http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.CDV.05.Pan_lysine_acetylation.AllCell.bed ...

  12. File list: His.Gon.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Gon.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Gonad ...SRX099893,SRX099896 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Gon.10.Pan_lysine_acetylation.AllCell.bed ...

  13. File list: His.Bon.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bon.20.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Bone ...http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bon.20.Pan_lysine_acetylation.AllCell.bed ...

  14. File list: His.Dig.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Dig.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Digest...ive tract http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Dig.10.Pan_lysine_acetylation.AllCell.bed ...

  15. File list: His.Bld.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Blood... http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.Pan_lysine_acetylation.AllCell.bed ...

  16. File list: His.Unc.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Unc.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Uncla...ssified http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Unc.50.Pan_lysine_acetylation.AllCell.bed ...

  17. File list: His.Utr.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Utr.05.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Uteru...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Utr.05.Pan_lysine_acetylation.AllCell.bed ...

  18. File list: His.Liv.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Liv.05.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Liver ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.05.Pan_lysine_acetylation.AllCell.bed ...

  19. File list: His.Dig.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Dig.20.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Diges...tive tract http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Dig.20.Pan_lysine_acetylation.AllCell.bed ...

  20. File list: His.ALL.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.ALL.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation All ce...ll types SRX099893,SRX099896 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.ALL.50.Pan_lysine_acetylation.AllCell.bed ...

  1. File list: His.Lng.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Lung h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Lng.10.Pan_lysine_acetylation.AllCell.bed ...

  2. File list: His.Liv.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Liv.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Liver ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.10.Pan_lysine_acetylation.AllCell.bed ...

  3. File list: His.Bld.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Blood ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.Pan_lysine_acetylation.AllCell.bed ...

  4. File list: His.Bld.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Blood ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.Pan_lysine_acetylation.AllCell.bed ...

  5. File list: His.Pan.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Pancr...eas http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Pan.10.Pan_lysine_acetylation.AllCell.bed ...

  6. File list: His.Epd.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Epd.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Epider...mis http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Epd.10.Pan_lysine_acetylation.AllCell.bed ...

  7. File list: His.Pan.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.50.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Pancr...eas http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Pan.50.Pan_lysine_acetylation.AllCell.bed ...

  8. File list: His.Oth.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Others... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.Pan_lysine_acetylation.AllCell.bed ...

  9. File list: His.PSC.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Plurip...otent stem cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.PSC.50.Pan_lysine_acetylation.AllCell.bed ...

  10. File list: His.Neu.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Neura...l http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.10.Pan_lysine_acetylation.AllCell.bed ...

  11. File list: His.ALL.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.ALL.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation All ce...ll types SRX099893,SRX099896 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.ALL.10.Pan_lysine_acetylation.AllCell.bed ...

  12. File list: His.Plc.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Plc.10.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Placen...ta http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Plc.10.Pan_lysine_acetylation.AllCell.bed ...

  13. File list: His.Plc.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Plc.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Place...nta http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Plc.10.Pan_lysine_acetylation.AllCell.bed ...

  14. File list: His.Prs.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Prs.10.Pan_lysine_acetylation.AllCell hg19 Histone Pan lysine acetylation Prost...ate http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Prs.10.Pan_lysine_acetylation.AllCell.bed ...

  15. File list: His.Bon.50.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bon.50.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Bone h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bon.50.Pan_lysine_acetylation.AllCell.bed ...

  16. File list: His.Oth.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Others... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.20.Pan_lysine_acetylation.AllCell.bed ...

  17. File list: His.Kid.05.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Kid.05.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Kidney... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Kid.05.Pan_lysine_acetylation.AllCell.bed ...

  18. File list: His.Myo.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Myo.20.Pan_lysine_acetylation.AllCell mm9 Histone Pan lysine acetylation Muscle... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Myo.20.Pan_lysine_acetylation.AllCell.bed ...

  19. File list: His.Lng.20.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins

    Directory of Open Access Journals (Sweden)

    Michael N. Davies

    2016-01-01

    Full Text Available Lysine acetylation (AcK, a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT, an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.

  8. Histone H3 acetylation in the postmortem Parkinson's disease primary motor cortex.

    Science.gov (United States)

    Gebremedhin, Kibrom G; Rademacher, David J

    2016-08-01

    Although the role of epigenetics in Parkinson's disease (PD) has not been extensively studied, α-synuclein, the main component of Lewy bodies, decreased histone H3 acetylation. Here, we determined if there were histone acetylation changes in the primary motor cortex which, according to the Braak model, is one of the last brain regions affected in PD. Net histone H3 acetylation, histone H3 lysine 9 (H3K9), histone H3 lysine 14 (H3K14), histone H3 lysine 18 (H3K18), and histone H3 lysine 23 (H3K23) acetylation was assessed in the primary motor cortex of those affected and unaffected by PD. There was net increase in histone H3 acetylation due to increased H3K14 and H3K18 acetylation. There was a decrease in H3K9 acetylation. No between-groups difference was detected in H3K23 acetylation. Relationships between Unified Lewy Body Staging scores and histone H3 acetylation and substantia nigra depigmentation scores and histone H3 acetylation were observed. No relationships were detected between postmortem interval and histone H3 acetylation and expired age and histone H3 acetylation. These correlational data support the notion that the histone H3 acetylation changes observed here are not due to the postmortem interval or aging. Instead, they are due to PD and/or factors that covary with PD. The data suggest enhanced gene transcription in the primary motor cortex of the PD brain due to increase H3K14 and H3K18 acetylation. This effect is partially offset by a decreased H3K9 acetylation, which might repress gene transcription. PMID:27241718

  9. ACETYLATION INCREASES EWS-FLI1 DNA BINDING AND TRANSCRIPTIONAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Silke eSchlottmann

    2012-09-01

    Full Text Available Ewing Sarcoma (ES is associated with a balanced chromosomal translocation that in most cases leads to the expression of the oncogenic fusion protein and transcription factor EWS-FLI1. EWS-FLI1 has been shown to be crucial for ES cell survival and tumor growth. However, its regulation is still enigmatic. To date, no functionally significant posttranslational modifications of EWS-FLI1 have been shown. Since ES are sensitive to histone deacetylase inhibitors, and these inhibitors are advancing in clinical trials, we sought to identify if EWS-FLI1 is directly acetylated. We convincingly show acetylation of the C-terminal FLI1 (FLI1-CTD domain, which is the DNA binding domain of EWS-FLI1. In vitro acetylation studies showed that acetylated FLI1-CTD has higher DNA binding activity than the non-acetylated protein. Over-expression of PCAF or treatment with histone deacetylase inhibitors (HDI increased the transcriptional activity of EWS-FLI1, when co-expressed in COS7 cells. However, our data that evaluates the acetylation of ful-length EWS-FLI1 remains unclear, despite creating acetylation specific antibodies to four potential acetylation sites. We conclude that EWS-FLI1 may either gain access to chromatin as a result of histone acetylation or undergo regulation by direct acetylation. These data should be considered when patients are treated with HDAC inhibitors. Further investigation of this phenomenon will reveal if this potential acetylation has an impact on tumor response.

  10. N-Acetyltransferase 2 (NAT2) in Tunisian Population: Correlation Between Acetylation Phenotype and Genotype

    International Nuclear Information System (INIS)

    One hundred tuberculous patients were studied during 2004-2005 to determine acetylation phenotype, frequent mutations of NAT2 gene and to compare acetylation phenotype with NAT2 genotype in Tunisian population. Acetylation phenotype was determined by determination of acetylation index. Five mutations of NAT2 gene were evaluated by PCR/RFLP. Results show bimodal distribution of acetylation SA and RA phenotype, 75% and 25% and genotype 56% and 44%, respectively. Ten NAT2 alleles were found, NAT2*4 being the major one. Thirty-two different genotypes were found (9 RA and 23 SA). The major one was NAT2*6 B/NAT2*4. The concordance value was 79%. A good sensibility (98, 2%) of acetylation test for SA detection was found. Thus, acetylation phenotype in SA is predicted with poor error risk. (author)

  11. Histone acetylation dependent energy landscapes in tri-nucleosome revealed by residue-resolved molecular simulations

    Science.gov (United States)

    Chang, Le; Takada, Shoji

    2016-01-01

    Histone tail acetylation is a key epigenetic marker that tends to open chromatin folding and activate transcription. Despite intensive studies, precise roles of individual lysine acetylation in chromatin folding have only been poorly understood. Here, we revealed structural dynamics of tri-nucleosomes with several histone tail acetylation states and analyzed histone tail interactions with DNA by performing molecular simulations at an unprecedentedly high resolution. We found versatile acetylation-dependent landscapes of tri-nucleosome. The H4 and H2A tail acetylation reduced the contact between the first and third nucleosomes mediated by the histone tails. The H3 tail acetylation reduced its interaction with neighboring linker DNAs resulting in increase of the distance between consecutive nucleosomes. Notably, two copies of the same histone in a single nucleosome have markedly asymmetric interactions with DNAs, suggesting specific pattern of nucleosome docking albeit high inherent flexibility. Estimated transcription factor accessibility was significantly high for the H4 tail acetylated structures. PMID:27698366

  12. The potential role of wood acetylation in climate change mitigation

    OpenAIRE

    Van der Lugt, P.; Vogtländer, J.G.; J. Alexander; Bongers, F.; Stebbins, H.

    2014-01-01

    In a carbon footprint assessment, the greenhouse gas emissions during the life cycle of a material can be measured, and compared to alternative products in terms of kg CO2 equivalent. If applied correctly, wood acetylation opens up a range of new innovative applications in which high performance yet carbon intensive non-renewable materials such as metals, plastics and concrete may be replaced by abundantly available nondurable wood species. To better understand the difference in greenhouse ga...

  13. 4-Acetyl-1H-pyrrole-2-carbaldehyde

    Directory of Open Access Journals (Sweden)

    Tao Sun

    2012-10-01

    Full Text Available The title compound, C7H7NO2, was synthesized via a one-pot Vilsmeier–Haack and subsequent Friedel–Crafts reaction. The pyrazole ring makes dihedral angles of 4.50 (9 and 2.06 (8°, respectively, with the aldehyde and acetyl groups. In the crystal, classical N—H...O hydrogen bonds and weak C—H...O interactions assemble the molecules into a chain along the b axis.

  14. Acetylation modification regulates GRP78 secretion in colon cancer cells.

    Science.gov (United States)

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  15. Acetylation modification regulates GRP78 secretion in colon cancer cells

    Science.gov (United States)

    Li, Zongwei; Zhuang, Ming; Zhang, Lichao; Zheng, Xingnan; Yang, Peng; Li, Zhuoyu

    2016-01-01

    High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors. PMID:27460191

  16. Astrocyte Reactivity Following Blast Exposure Involves Aberrant Histone Acetylation

    Science.gov (United States)

    Bailey, Zachary S.; Grinter, Michael B.; VandeVord, Pamela J.

    2016-01-01

    Blast induced neurotrauma (BINT) is a prevalent injury within military and civilian populations. The injury is characterized by persistent inflammation at the cellular level which manifests as a multitude of cognitive and functional impairments. Epigenetic regulation of transcription offers an important control mechanism for gene expression and cellular function which may underlie chronic inflammation and result in neurodegeneration. We hypothesize that altered histone acetylation patterns may be involved in blast induced inflammation and the chronic activation of glial cells. This study aimed to elucidate changes to histone acetylation occurring following injury and the roles these changes may have within the pathology. Sprague Dawley rats were subjected to either a 10 or 17 psi blast overpressure within an Advanced Blast Simulator (ABS). Sham animals underwent the same procedures without blast exposure. Memory impairments were measured using the Novel Object Recognition (NOR) test at 2 and 7 days post-injury. Tissues were collected at 7 days for Western blot and immunohistochemistry (IHC) analysis. Sham animals showed intact memory at each time point. The novel object discrimination decreased significantly between two and 7 days for each injury group (p processes. We have shown aberrant histone acetylation patterns involved in blast induced astrogliosis and cognitive impairments. Further understanding of their role in the injury progression may lead to novel therapeutic targets. PMID:27551260

  17. Selective cleavage enhanced by acetylating the side chain of lysine.

    Science.gov (United States)

    Fu, Leixiaomeng; Chen, Tingting; Xue, Gaiqing; Zu, Lily; Fang, Weihai

    2013-01-01

    Selective cleavage is of great interest in mass spectrometry studies as it can help sequence identification by promoting simple fragmentation pattern of peptides and proteins. In this work, the collision-induced dissociation of peptides containing internal lysine and acetylated lysine residues were studied. The experimental and computational results revealed that multiple fragmentation pathways coexisted when the lysine residue was two amino acid residues away from N-terminal of the peptide. After acetylation of the lysine side-chain, b(n)+ ions were the most abundant primary fragment products and the Lys(Ac)-Gly amide bond became the dominant cleavage site via an oxazolone pathway. Acetylating the side-chain of lysine promoted the selective cleavage of Lys-Xxx amide bond and generated much more information of the peptide backbone sequence. The results re-evaluate the selective cleavage due to the lysine basic side-chain and provide information for studying the post-translational modification of proteins and other bio-molecules containing Lys residues. PMID:23303756

  18. PURIFICATION OF L-METHIONINE AND N-ACETYL-D-METHIONINE FROM THE MIXTURE OF ENZYMATICALLY DEACYLATED N-ACETYL-DL-METHIONINE

    Institute of Scientific and Technical Information of China (English)

    YAN Xiaomin; ZHAO Lin; SHAO Jianhui; TAN Xin; SONG Zhengxiao

    2004-01-01

    N-acetyl-D-methionine, NaAc and the remains of N-acetyl-L-methionine dramatically affect the purification of L-methionine when purified from the mixture of enzymatically deacylated N-acetyl-DL-methionine, leading to a low yield conventionally. Here, this paper reports a successful separation and purification of both L-methionine and N-acetyl-D-methionine by an H ion-exchange column. The pH, L-Met concentration and the ratio between the content of sodium cation and the ion-exchange capacity were optimized to obtain the maximum yield. Experimental results indicate that, under the optimized conditions, the yields of L-methionine and N-acetyl-D-methionine can reach as high as 85% and 75%, respectively.

  19. Cell differentiation along multiple pathways accompanied by changes in histone acetylation status.

    Science.gov (United States)

    Legartová, Soňa; Kozubek, Stanislav; Franek, Michal; Zdráhal, Zbyněk; Lochmanová, Gabriela; Martinet, Nadine; Bártová, Eva

    2014-04-01

    Post-translational modification of histones is fundamental to the regulation of basic nuclear processes and subsequent cellular events, including differentiation. In this study, we analyzed acetylated forms of histones H2A, H2B, and H4 during induced differentiation in mouse (mESCs) and human (hESCs) embryonic stem cells and during induced enterocytic differentiation of colon cancer cells in vitro. Endoderm-like differentiation of mESCs induced by retinoic acid and enterocytic differentiation induced by histone deacetylase inhibitor sodium butyrate were accompanied by increased mono-, di-, and tri-acetylation of histone H2B and a pronounced increase in di- and tri-acetylation of histone H4. In enterocytes, mono-acetylation of histone H2A also increased and tetra-acetylation of histone H4 appeared only after induction of this differentiation pathway. During differentiation of hESCs, we observed increased mono-acetylation and decreased tri-acetylation of H2B. Mono-, di-, and tri-acetylation of H4 were reduced, manifested by a significant increase in nonacetylated H4 histones. Levels of acetylated histones increased during induced differentiation in mESCs and during histone deacetylase (HDAC) inhibitor-induced enterocytic differentiation, whereas differentiation of human ESCs was associated with reduced acetylation of histones H2B and H4.

  20. Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.

    Science.gov (United States)

    Feng, Y; Rustan, T D; Ferguson, R J; Doll, M A; Hein, D W

    1994-01-01

    Arylamine-hemoglobin adducts are a valuable dosimeter for assessing arylamine exposures and carcinogenic risk. The effects of age, sex, time-course, dose, and acetylator genotype on levels of 2-aminofluorene-hemoglobin adducts were investigated in homozygous rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Pats) acetylator hamsters congenic at the polymorphic (NAT2) acetylator locus. Following administration of a single ip dose of [3H]2-aminofluorene, peak 2-aminofluorene-hemoglobin adduct levels were achieved at 12-18 hr and retained a plateau up to 72 hr postinjection in both rapid and slow acetylator congenic hamsters. 2-Aminofluorene-hemoglobin adduct levels did not differ significantly between young (5-6 weeks) and old (32-49 weeks) hamsters or between male and female hamsters within either acetylator genotype. 2-Aminofluorene-hemoglobin adduct levels increased in a dose-dependent manner (r = 0.95, p = 0.0001) and were consistently higher in slow versus rapid acetylator congenic hamsters in studies of both time-course and dose-effect. The magnitude of the acetylator genotype-dependent difference was a function of dose; 2-aminofluorene-hemoglobin adduct levels were 1.5-fold higher in slow acetylator congenic hamsters following a 60 mg/kg 2-aminofluorene dose (p = 0.0013) but 2-fold higher following a 100 mg/kg 2-aminofluorene dose (p < 0.0001). These results show a specific and significant role for NAT2 acetylator genotype in formation of arylamine-hemoglobin adducts, which may reflect the relationship between acetylator genotype and the incidence of different cancers from arylamine exposures. PMID:8291051

  1. A random sequential mechanism of aminoglycoside acetylation by Mycobacterium tuberculosis Eis protein.

    Directory of Open Access Journals (Sweden)

    Oleg V Tsodikov

    Full Text Available An important cause of bacterial resistance to aminoglycoside antibiotics is the enzymatic acetylation of their amino groups by acetyltransferases, which abolishes their binding to and inhibition of the bacterial ribosome. Enhanced intracellular survival (Eis protein from Mycobacterium tuberculosis (Mt is one of such acetyltransferases, whose upregulation was recently established as a cause of resistance to aminoglycosides in clinical cases of drug-resistant tuberculosis. The mechanism of aminoglycoside acetylation by MtEis is not completely understood. A systematic analysis of steady-state kinetics of acetylation of kanamycin A and neomycin B by Eis as a function of concentrations of these aminoglycosides and the acetyl donor, acetyl coenzyme A, reveals that MtEis employs a random-sequential bisubstrate mechanism of acetylation and yields the values of the kinetic parameters of this mechanism. The implications of these mechanistic properties for the design of inhibitors of Eis and other aminoglycoside acetyltransferases are discussed.

  2. Acetylated starch nanocrystals: Preparation and antitumor drug delivery study.

    Science.gov (United States)

    Xiao, Huaxi; Yang, Tao; Lin, Qinlu; Liu, Gao-Qiang; Zhang, Lin; Yu, Fengxiang; Chen, Yuejiao

    2016-08-01

    In this study, we developed a new nanoparticulate system for acetylated starch nanocrystals (ASN) using broken rice. ASN with different degrees of substitution (DS) of 0.04, 0.08 and 0.14 were prepared using acetic anhydride as acetylating agent through reaction with starch nanocrystals (SN). The resulting ASN were investigated for the capability to load and release doxorubicin hydrochloride (DOX), and the antitumor activities of DOX-loaded SN and DOX-loaded ASN were evaluated as potential drug delivery systems for cancer therapy. Cellular uptake and cytotoxicity of nanocrystals and the DOX-loaded nanocrystals were investigated using fluorescence microscopy and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Compared with acetylated starches (AS) and native starches (NS), ASN with DS 0.14 loaded up to 6.07% of DOX with a higher loading efficiency of 91.1% and had steadier drug-release rates. Toxicity analysis using the rat hepatocytes model suggested that ASN was biocompatible and could be used for drug delivery. Furthermore, ASN were taken up by cancer cells in vitro and significantly enhanced the cytotoxicity of DOX against HeLa human cervical carcinoma cells. The IC50 value of DOX-loaded ASN-DS 0.14 was 3.8μg/mL for 24h of treatment, which was significantly lower than that of free DOX (21μg/mL). These results indicate that the prepared ASN using broken rice is a promising vehicle for the controlled delivery of DOX for cancer therapy. PMID:27156696

  3. Acetyl hexapeptide-3 in a cosmetic formulation acts on skin mechanical properties - clinical study

    OpenAIRE

    Kassandra Azevedo Tadini; Daiane Garcia Mercurio; Patrícia Maria Berardo Gonçalves Maia Campos

    2015-01-01

    abstract Acetyl hexapeptide-3 has been used in anti-aging topical formulations aimed at improving skin appearance. However, few basic studies address its effects on epidermis and dermis, when vehiculated in topical formulations. Thus, the objective of this study was to determine the clinical efficacy of acetyl hexapeptide-3 using biophysical techniques. For this purpose, formulations with and without acetyl hexapeptide-3 were applied to the ventral forearm and the face area of forty female vo...

  4. Core promoter acetylation is not required for high transcription from the phosphoenolpyruvate carboxylase promoter in maize

    Directory of Open Access Journals (Sweden)

    Horst Ina

    2009-12-01

    Full Text Available Abstract Background Acetylation of promoter nucleosomes is tightly correlated and mechanistically linked to gene activity. However, transcription is not necessary for promoter acetylation. It seems, therefore, that external and endogenous stimuli control histone acetylation and by this contribute to gene regulation. Photosynthetic genes in plants are excellent models with which to study the connection between stimuli and chromatin modifications because these genes are strongly expressed and regulated by multiple stimuli that are easily manipulated. We have previously shown that acetylation of specific histone lysine residues on the photosynthetic phosphoenolpyruvate carboxylase (Pepc promoter in maize is controlled by light and is independent of other stimuli or gene activity. Acetylation of upstream promoter regions responds to a set of other stimuli which include the nutrient availability of the plant. Here, we have extended these studies by analysing histone acetylation during the diurnal and circadian rhythm of the plant. Results We show that histone acetylation of individual lysine residues is removed from the core promoter before the end of the illumination period which is an indication that light is not the only factor influencing core promoter acetylation. Deacetylation is accompanied by a decrease in gene activity. Pharmacological inhibition of histone deacetylation is not sufficient to prevent transcriptional repression, indicating that deacetylation is not controlling diurnal gene regulation. Variation of the Pepc promoter activity during the day is controlled by the circadian oscillator as it is maintained under constant illumination for at least 3 days. During this period, light-induced changes in histone acetylation are completely removed from the core promoter, although the light stimulus is continuously applied. However, acetylation of most sites on upstream promoter elements follows the circadian rhythm. Conclusion Our results

  5. Autoimmune regulator is acetylated by transcription coactivator CBP/p300

    Energy Technology Data Exchange (ETDEWEB)

    Saare, Mario, E-mail: mario.saare@ut.ee [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); Rebane, Ana [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia); SIAF, Swiss Institute of Allergy and Asthma Research, University of Zuerich, Davos (Switzerland); Rajashekar, Balaji; Vilo, Jaak [BIIT, Bioinformatics, Algorithmics and Data Mining group, Institute of Computer Science, University of Tartu, Tartu (Estonia); Peterson, Paert [Molecular Pathology, Institute of General and Molecular Pathology, University of Tartu, 19th Ravila Str, Tartu (Estonia)

    2012-08-15

    The Autoimmune Regulator (AIRE) is a regulator of transcription in the thymic medulla, where it controls the expression of a large set of peripheral-tissue specific genes. AIRE interacts with the transcriptional coactivator and acetyltransferase CBP and synergistically cooperates with it in transcriptional activation. Here, we aimed to study a possible role of AIRE acetylation in the modulation of its activity. We found that AIRE is acetylated in tissue culture cells and this acetylation is enhanced by overexpression of CBP and the CBP paralog p300. The acetylated lysines were located within nuclear localization signal and SAND domain. AIRE with mutations that mimicked acetylated K243 and K253 in the SAND domain had reduced transactivation activity and accumulated into fewer and larger nuclear bodies, whereas mutations that mimicked the unacetylated lysines were functionally similar to wild-type AIRE. Analogously to CBP, p300 localized to AIRE-containing nuclear bodies, however, the overexpression of p300 did not enhance the transcriptional activation of AIRE-regulated genes. Further studies showed that overexpression of p300 stabilized the AIRE protein. Interestingly, gene expression profiling revealed that AIRE, with mutations mimicking K243/K253 acetylation in SAND, was able to activate gene expression, although the affected genes were different and the activation level was lower from those regulated by wild-type AIRE. Our results suggest that the AIRE acetylation can influence the selection of AIRE activated genes. -- Highlights: Black-Right-Pointing-Pointer AIRE is acetylated by the acetyltransferases p300 and CBP. Black-Right-Pointing-Pointer Acetylation occurs between CARD and SAND domains and within the SAND domain. Black-Right-Pointing-Pointer Acetylation increases the size of AIRE nuclear dots. Black-Right-Pointing-Pointer Acetylation increases AIRE protein stability. Black-Right-Pointing-Pointer AIRE acetylation mimic regulates a different set of AIRE

  6. p53 targets simian virus 40 large T antigen for acetylation by CBP.

    Science.gov (United States)

    Poulin, Danielle L; Kung, Andrew L; DeCaprio, James A

    2004-08-01

    Simian virus 40 (SV40) large T antigen (T Ag) interacts with the tumor suppressor p53 and the transcriptional coactivators CBP and p300. Binding of these cellular proteins in a ternary complex has been implicated in T Ag-mediated transformation. It has been suggested that the ability of CBP/p300 to modulate p53 function underlies p53's regulation of cell proliferation and tumorigenesis. In this study, we provide further evidence that CBP activity may be mediated through its synergistic action with p53. We demonstrate that SV40 T Ag is acetylated in vivo in a p53-dependent manner and T Ag acetylation is largely mediated by CBP. The acetylation of T Ag is dependent on its interaction with p53 and on p53's interaction with CBP. We have mapped the site of acetylation on T Ag to the C-terminal lysine residue 697. This acetylation site is conserved between the T antigens of the human polyomaviruses JC and BK, which are also known to interact with p53. We show that both JC and BK T antigens are also acetylated at corresponding sites in vivo. While other proteins are known to be acetylated by CBP/p300, none are known to depend on p53 for acetylation. T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function. PMID:15254196

  7. Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juhyung; Yun, Nuri; Kim, Chiho [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Song, Min-Young; Park, Kang-Sik [Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701 (Korea, Republic of); Oh, Young J., E-mail: yjoh@yonsei.ac.kr [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)

    2014-04-25

    Highlights: • Cyclin-dependent kinase 5 (CDK5) is present as an acetylated form. • CDK5 is acetylated by GCN5. • CDK5’s acetylation site is mapped at Lys33. • Its acetylation may affect CDK5’s kinase activity. - Abstract: Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.

  8. Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells

    International Nuclear Information System (INIS)

    Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium. (author)

  9. Partial acetylation in situ of cellulosic fabric and its resistance to microbial and actinic degradation

    Directory of Open Access Journals (Sweden)

    K. L. Maheshwari

    1963-04-01

    Full Text Available Partial acetylation in situ of cotton fabrics can be achieved satisfactorily when it is carried out using 0.03 percent perchloricacid as the catalyst at a temperature not exceeding 30DegreeC. Increase in concentration of perchloric acid or temperature adversely affects the tensile strength of the fabrics. The acetylation of fabrics confers resistance to leaching. Scouring of the fabric prior to acetylation does not materially influence the extent of substitution of hydroxyl groups by acetyl ones. The acetylating mixture can be repeatedly used but fresh addition of the catalyst is necessary. With increase in the period of acetylation or in the quantity of catalyst, there is a progressive increase in acetic acid yield but the tensile strength of the fabric shows a corresponding decrease. Partial acetylation affords protection against microbial attack when the acetyl content of the acetylated fabrics is 14-15 percent. The treatment does not however afford protection against degradation by artificial light, or sunlight or weathering.

  10. Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism.

    Science.gov (United States)

    You, Di; Yin, Bin-Cheng; Li, Zhi-Hai; Zhou, Ying; Yu, Wen-Bang; Zuo, Peng; Ye, Bang-Ce

    2016-06-14

    In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-β) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR-DNA binding. It was observed that this regulatory function of acetylated GSI-β enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes. PMID:27247389

  11. Synthesis of Andrographolide Glucopyranoside and Selective Cleavage of O-acetyl Groups in Sugar Moiety

    Institute of Scientific and Technical Information of China (English)

    WANG Shao-Min; LIU Hong-Min

    2008-01-01

    Andrographolide glucopyranosides were synthesized from andrographolide and tetra-O-acetyl-β-D-glucopyranosyl bromide via a Koenigs-Knorr reaction and deacetylation with a moderate deacetylation reagent dibutyltin oxide in methanol for the first time.The structures of the andrographolide derivatives were confirmed by IR, NMR,and HRMS.Deprotection of the acetylated andrographolide glucopyranoside with dibutyltin oxide in methanol selectively removed all acetyl groups of the sugar moiety, whereas the acetyl group of the andrographolide part and the base- or acid-sensitive functional groups were retained.

  12. Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer, in Danish postmenopausal women

    DEFF Research Database (Denmark)

    Egeberg, Rikke; Olsen, Anja; Autrup, Herman;

    2008-01-01

    total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (P-interaction=0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has......The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study...... increment in intake. Compared with slow acetylators, the IRR (95% confidence interval) among fast N-acetyl transferase 1 acetylators was 1.43 (1.03-1.99) and 1.13 (0.83-1.54) among intermediate/fast N-acetyl transferase 2 acetylators. Interaction analyses revealed that the positive associations between...

  13. Comparative analysis of pharmacological treatments with N-acetyl-dl-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

    Science.gov (United States)

    Tighilet, Brahim; Leonard, Jacques; Bernard-Demanze, Laurence; Lacour, Michel

    2015-12-15

    Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only. PMID:26607469

  14. A reactivity-selectivity study of the Friedel-Crafts acetylation of 3,3′-dimethylbiphenyl and the oxidation of the acetyl derivatives

    DEFF Research Database (Denmark)

    Titinchi, Salam JJ; Kamounah, Fadhil S.; Abbo, Hanna S.;

    2012-01-01

    Background: Friedel-Crafts acetylation is an important route to aromatic ketones, in research laboratories and in industry. The acetyl derivatives of 3,3'-dimethylbiphenyl (3,3'-dmbp) have applications in the field of liquid crystals and polymers and may be oxidized to the dicarboxylic acids...... converted to the carboxylic acids by hypochlorite oxidation. The relative stabilities of the isomeric products and the corresponding s-complexes were studied by DFT calculations and the data indicated that mono-and diacetylation followed different mechanisms. Conclusions: Friedel-Crafts acetylation of 3...

  15. The Metabolic Fate of Deoxynivalenol and Its Acetylated Derivatives in a Wheat Suspension Culture: Identification and Detection of DON-15-O-Glucoside, 15-Acetyl-DON-3-O-Glucoside and 15-Acetyl-DON-3-Sulfate

    Directory of Open Access Journals (Sweden)

    Clemens Schmeitzl

    2015-08-01

    Full Text Available Deoxynivalenol (DON is a protein synthesis inhibitor produced by the Fusarium species, which frequently contaminates grains used for human or animal consumption. We treated a wheat suspension culture with DON or one of its acetylated derivatives, 3-acetyl-DON (3-ADON, 15-acetyl-DON (15-ADON and 3,15-diacetyl-DON (3,15-diADON, and monitored the metabolization over a course of 96 h. Supernatant and cell extract samples were analyzed using a tailored LC-MS/MS method for the quantification of DON metabolites. We report the formation of tentatively identified DON-15-O-β-D-glucoside (D15G and of 15-acetyl-DON-3-sulfate (15-ADON3S as novel deoxynivalenol metabolites in wheat. Furthermore, we found that the recently identified 15-acetyl-DON-3-O-β-D-glucoside (15-ADON3G is the major metabolite produced after 15-ADON challenge. 3-ADON treatment led to a higher intracellular content of toxic metabolites after six hours compared to all other treatments. 3-ADON was exclusively metabolized into DON before phase II reactions occurred. In contrast, we found that 15-ADON was directly converted into 15-ADON3G and 15-ADON3S in addition to metabolization into deoxynivalenol-3-O-β-D-glucoside (D3G. This study highlights significant differences in the metabolization of DON and its acetylated derivatives.

  16. The dynamic organization of fungal acetyl-CoA carboxylase

    Science.gov (United States)

    Hunkeler, Moritz; Stuttfeld, Edward; Hagmann, Anna; Imseng, Stefan; Maier, Timm

    2016-04-01

    Acetyl-CoA carboxylases (ACCs) catalyse the committed step in fatty-acid biosynthesis: the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. They are important regulatory hubs for metabolic control and relevant drug targets for the treatment of the metabolic syndrome and cancer. Eukaryotic ACCs are single-chain multienzymes characterized by a large, non-catalytic central domain (CD), whose role in ACC regulation remains poorly characterized. Here we report the crystal structure of the yeast ACC CD, revealing a unique four-domain organization. A regulatory loop, which is phosphorylated at the key functional phosphorylation site of fungal ACC, wedges into a crevice between two domains of CD. Combining the yeast CD structure with intermediate and low-resolution data of larger fragments up to intact ACCs provides a comprehensive characterization of the dynamic fungal ACC architecture. In contrast to related carboxylases, large-scale conformational changes are required for substrate turnover, and are mediated by the CD under phosphorylation control.

  17. Changes in acetyl CoA levels during the early embryonic development of Xenopus laevis.

    Science.gov (United States)

    Tsuchiya, Yugo; Pham, Uyen; Hu, Wanzhou; Ohnuma, Shin-Ichi; Gout, Ivan

    2014-01-01

    Coenzyme A (CoA) is a ubiquitous and fundamental intracellular cofactor. CoA acts as a carrier of metabolically important carboxylic acids in the form of CoA thioesters and is an obligatory component of a multitude of catabolic and anabolic reactions. Acetyl CoA is a CoA thioester derived from catabolism of all major carbon fuels. This metabolite is at a metabolic crossroads, either being further metabolised as an energy source or used as a building block for biosynthesis of lipids and cholesterol. In addition, acetyl CoA serves as the acetyl donor in protein acetylation reactions, linking metabolism to protein post-translational modifications. Recent studies in yeast and cultured mammalian cells have suggested that the intracellular level of acetyl CoA may play a role in the regulation of cell growth, proliferation and apoptosis, by affecting protein acetylation reactions. Yet, how the levels of this metabolite change in vivo during the development of a vertebrate is not known. We measured levels of acetyl CoA, free CoA and total short chain CoA esters during the early embryonic development of Xenopus laevis using HPLC. Acetyl CoA and total short chain CoA esters start to increase around midblastula transition (MBT) and continue to increase through stages of gastrulation, neurulation and early organogenesis. Pre-MBT embryos contain more free CoA relative to acetyl CoA but there is a shift in the ratio of acetyl CoA to CoA after MBT, suggesting a metabolic transition that results in net accumulation of acetyl CoA. At the whole-embryo level, there is an apparent correlation between the levels of acetyl CoA and levels of acetylation of a number of proteins including histones H3 and H2B. This suggests the level of acetyl CoA may be a factor, which determines the degree of acetylation of these proteins, hence may play a role in the regulation of embryogenesis. PMID:24831956

  18. Changes in acetyl CoA levels during the early embryonic development of Xenopus laevis.

    Directory of Open Access Journals (Sweden)

    Yugo Tsuchiya

    Full Text Available Coenzyme A (CoA is a ubiquitous and fundamental intracellular cofactor. CoA acts as a carrier of metabolically important carboxylic acids in the form of CoA thioesters and is an obligatory component of a multitude of catabolic and anabolic reactions. Acetyl CoA is a CoA thioester derived from catabolism of all major carbon fuels. This metabolite is at a metabolic crossroads, either being further metabolised as an energy source or used as a building block for biosynthesis of lipids and cholesterol. In addition, acetyl CoA serves as the acetyl donor in protein acetylation reactions, linking metabolism to protein post-translational modifications. Recent studies in yeast and cultured mammalian cells have suggested that the intracellular level of acetyl CoA may play a role in the regulation of cell growth, proliferation and apoptosis, by affecting protein acetylation reactions. Yet, how the levels of this metabolite change in vivo during the development of a vertebrate is not known. We measured levels of acetyl CoA, free CoA and total short chain CoA esters during the early embryonic development of Xenopus laevis using HPLC. Acetyl CoA and total short chain CoA esters start to increase around midblastula transition (MBT and continue to increase through stages of gastrulation, neurulation and early organogenesis. Pre-MBT embryos contain more free CoA relative to acetyl CoA but there is a shift in the ratio of acetyl CoA to CoA after MBT, suggesting a metabolic transition that results in net accumulation of acetyl CoA. At the whole-embryo level, there is an apparent correlation between the levels of acetyl CoA and levels of acetylation of a number of proteins including histones H3 and H2B. This suggests the level of acetyl CoA may be a factor, which determines the degree of acetylation of these proteins, hence may play a role in the regulation of embryogenesis.

  19. Location of the O-acetyl substituents on a nonasaccharide repeating unit of sycamore extracellular xyloglucan.

    Science.gov (United States)

    York, W S; Oates, J E; van Halbeek, H; Darvill, A G; Albersheim, P; Tiller, P R; Dell, A

    1988-02-15

    The locations of the O-acetyl substituents on the major nonasaccharide repeating unit of the xyloglucan isolated from sycamore extracellular polysaccharides were determined by a combination of analytical methods, including f.a.b.-m.s. and 1H-n.m.r. spectroscopy. The O-2-linked-beta-D-galactosyl residue of the nonasaccharide was found to be the dominant site of O-acetyl substitution. Both mono-O-acetylated and di-O-acetylated beta-D-galactosyl residues were detected. The degree of O-acetylation of the beta-D-galactosyl residue, was estimated by 1H-n.m.r. spectroscopy to be 55-60% at O-6, 15-20% at O-4, and 20-25% at O-3. 1H-n.m.r. spectroscopy also indicated that approximately 50% of the beta-D-galactosyl residues are mono-O-acetylated, 25-30% are di-O-acetylated, and 20% are not acetylated.

  20. Lysine acetylation targets protein complexes and co-regulates major cellular functions

    DEFF Research Database (Denmark)

    Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian;

    2009-01-01

    Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600 ly...

  1. A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.

    Science.gov (United States)

    Kim, Dong-Hyun; Xiao, Zhen; Kwon, Sanghoon; Sun, Xiaoxiao; Ryerson, Daniel; Tkac, David; Ma, Ping; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Zhou, Edward; Xu, H Eric; Palvimo, Jorma J; Chen, Lin-Feng; Kemper, Byron; Kemper, Jongsook Kim

    2015-01-13

    Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and acetylation-defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-κB but blocked that with RXRα, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXRα target genes. A dysregulated acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders. PMID:25425577

  2. Nε-lysine acetylation of a bacterial transcription factor inhibits Its DNA-binding activity.

    Directory of Open Access Journals (Sweden)

    Sandy Thao

    Full Text Available Evidence suggesting that eukaryotes and archaea use reversible N(ε-lysine (N(ε-Lys acetylation to modulate gene expression has been reported, but evidence for bacterial use of N(ε-Lys acetylation for this purpose is lacking. Here, we report data in support of the notion that bacteria can control gene expression by modulating the acetylation state of transcription factors (TFs. We screened the E. coli proteome for substrates of the bacterial Gcn5-like protein acetyltransferase (Pat. Pat acetylated four TFs, including the RcsB global regulatory protein, which controls cell division, and capsule and flagellum biosynthesis in many bacteria. Pat acetylated residue Lys180 of RcsB, and the NAD(+-dependent Sir2 (sirtuin-like protein deacetylase (CobB deacetylated acetylated RcsB (RcsB(Ac, demonstrating that N(ε-Lys acetylation of RcsB is reversible. Analysis of RcsB(Ac and variant RcsB proteins carrying substitutions at Lys180 provided biochemical and physiological evidence implicating Lys180 as a critical residue for RcsB DNA-binding activity. These findings further the likelihood that reversible N(ε-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells.

  3. Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns

    DEFF Research Database (Denmark)

    Lundby, Alicia; Hansen, Kasper Lage; Weinert, Brian Tate;

    2012-01-01

    Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,54...

  4. The Effect of Acetyl-L-Carnitine Administration on Persons with Down Syndrome

    Science.gov (United States)

    Pueschel, Siegfried M.

    2006-01-01

    Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and…

  5. Acetylation of Starch with Vinyl Acetate in Imidazolium Ionic Liquids and Characterization of Acetate Distribution

    Science.gov (United States)

    Starch was acetylated with vinyl acetate in different 1-butyl-3-methylimidazolium (BMIM) salts as solvent in effort to produce starches with different acetylation patterns. Overall degree of substitution was much higher for basic anions such as acetate and dicyanimide (dca) than for neutral anions ...

  6. chiral Synthesis of 13-Acetyl-12-hydroxy-podocarpane-8, 11,13-triene-7-one

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    An enantioselective synthetic route to (+)-13-acetyl-12-hydroxy-podocarpane-8,11,13-triene-7-one 1a and (-)-13-acetyl-12-hydroxy-podocarpane-8,11,13-triene-7-one 1b was developed from (S)-(-)-a -cyclocitral 8a and (R)-(+)-a -cyclocitral 8b.

  7. Histone Acetylation is Recruited in Consolidation as a Molecular Feature of Stronger Memories

    Science.gov (United States)

    Federman, Noel; Fustinana, Maria Sol; Romano, Arturo

    2009-01-01

    Gene expression is a key process for memory consolidation. Recently, the participation of epigenetic mechanisms like histone acetylation was evidenced in long-term memories. However, until now the training strength required and the persistence of the chromatin acetylation recruited are not well characterized. Here we studied whether histone…

  8. Alamethicin biosynthesis: acetylation of the amino terminus and attachment of phenylalaninol.

    Science.gov (United States)

    Mohr, H; Kleinkauf, H

    1978-10-12

    Alamethicin synthetase was extracted from the fungus Trichoderma viride at the end of its exponential growth phase. It is multienzyme complex with a molecular weight of approx. 480 000. The biosynthesis of alamethicin is initiated on the synthetase by acetylation of thiolester-bound aminoisobutyric acid, which remains enzyme bound. Acetyl-CoA serves as the acetate donor. Of the alamethicin constituents, glycine, alanine and valine are also acetylated when incubated alone. This acetylation is prevented by added aminoisobutyric acid, which indicates that the site on alamethicin synthetase catalyzing the acetylation has a preference for aminoisobutyric acid. Alamethicin formation on the synthetase is terminated by linkage of phenylalaninol to the carboxyl terminus of the peptide. It is unlikely that the amino alcohol is a degradation product of alamethicin or that it had been split off from the synthetase complex. Thus it is probably the reaction product of a separate enzyme system. PMID:568941

  9. Effect of Acetyl Group on Mechanical Properties of Chitin/Chitosan Nanocrystal: A Molecular Dynamics Study

    Directory of Open Access Journals (Sweden)

    Junhe Cui

    2016-01-01

    Full Text Available Chitin fiber is the load-bearing component in natural chitin-based materials. In these materials, chitin is always partially deacetylated to different levels, leading to diverse material properties. In order to understand how the acetyl group enhances the fracture resistance capability of chitin fiber, we constructed atomistic models of chitin with varied acetylation degree and analyzed the hydrogen bonding pattern, fracture, and stress-strain behavior of these models. We notice that the acetyl group can contribute to the formation of hydrogen bonds that can stabilize the crystalline structure. In addition, it is found that the specimen with a higher acetylation degree presents a greater resistance against fracture. This study describes the role of the functional group, acetyl groups, in crystalline chitin. Such information could provide preliminary understanding of nanomaterials when similar functional groups are encountered.

  10. Effects of Partially N-acetylated Chitosans to Elicit Resistance Reaction on Brassica napus L.

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-kun; TANG Zhang-lin; CHEN Li; GUO Yi-hong; CHEN Yun-ping; LI Jia-na

    2002-01-01

    The effects to elicit resistance reaction on oilseed rape (Brassica napus L. cv Xinongchangjiao )by four partially N-acetylated chitosan 7B, 8B, 9B and 10B (Degree of acetylation (D. A. ) is 30%, 20%,10%, 0%, respectively) and Glycol chitosan (GC, D.A. is 0%) were investigated and compared. Results showed that chitosan were similar to salicylic acid (SA), and could induce resistance reaction, but the reaction was influenced by the degree of acetylation of chitosan. Fully deacetylated chitosans, 10B and GC, elicited chitinase activity, but partially acetylated chitosan, 7B, 8B and 9B, inhibited chitinase activity. Phenyalanine ammonia-lyase (PAL) was also elicited. Elicitor activity increased with on increasing degree of acetylation, 7B induced highest PAL activity among all chitosans. All chitosans induced peroxidase (POD) in a similar level.After elicited by glycol chitosan, like SA treatment, the seedlings increased disease resistance to Sclerotinia sclerotiorum significantly.

  11. Acetylation of barnyardgrass starch with acetic anhydride under iodine catalysis.

    Science.gov (United States)

    Bartz, Josiane; Goebel, Jorge Tiago; Giovanaz, Marcos Antônio; Zavareze, Elessandra da Rosa; Schirmer, Manoel Artigas; Dias, Alvaro Renato Guerra

    2015-07-01

    Barnyardgrass (Echinochloa crus-galli) is an invasive plant that is difficult to control and is found in abundance as part of the waste of the paddy industry. In this study, barnyardgrass starch was extracted and studied to obtain a novel starch with potential food and non-food applications. We report some of the physicochemical, functional and morphological properties as well as the effect of modifying this starch with acetic anhydride by catalysis with 1, 5 or 10mM of iodine. The extent of the introduction of acetyl groups increased with increasing iodine levels as catalyst. The shape of the granules remained unaltered, but there were low levels of surface corrosion and the overall relative crystallinity decreased. The pasting temperature, enthalpy and other gelatinisation temperatures were reduced by the modification. There was an increase in the viscosity of the pastes, except for the peak viscosity, which was strongly reduced in 10mM iodine.

  12. Acetylated Lysozyme as Impurity in Lysozyme Crystals: Constant Distribution Coefficient

    Science.gov (United States)

    Thomas, B. R.; Chernov, A. A.

    2000-01-01

    Hen egg white lysozyme (HEWL) was acetylated to modify molecular charge keeping the molecular size and weight nearly constant. Two derivatives, A and B, more and less acetylated, respectively, were obtained, separated, purified and added to the solution from which crystals of tetragonal HEWL crystals were grown. Amounts of the A or B impurities added were 0.76, 0.38 and 0.1 milligram per millimeter while HEWL concentration were 20, 30 and 40 milligram per milliliter. The crystals grown in 18 experiments for each impurity were dissolved and quantities of A or B additives in these crystals were analyzed by cation exchange high performance liquid chromatography. All the data for each set of 18 samples with the different impurity and regular HEWL concentrations is well described by one distribution coefficient K = 2.15 plus or minus 0.13 for A and K = 3.42 plus or minus 0.25 for B. The observed independence of the distribution coefficient on both the impurity concentration and supersaturation is explained by the dilution model described in this paper. It shows that impurity adsorption and incorporation rate is proportional to the impurity concentration and that the growth rate is proportional to the crystallizing protein in solution. With the kinetic coefficient for crystallization, beta = 5.10(exp -7) centimeters per second, the frequency at which an impurity molecule near the growing interface irreversibly joins a molecular site on the crystal was found to be 3 1 per second, much higher than the average frequency for crystal molecules. For best quality protein crystals it is better to have low microheterogeneous protein impurity concentration and high supers aturation.

  13. Antioxidant activity of N-acetyl-glucosamine based thiazolidine derivative

    Institute of Scientific and Technical Information of China (English)

    Li Chunlei; Yang Yan; Han Baoqin; Liu Wanshun

    2007-01-01

    N-acetyl-glucosamine,the monomer of chitin,was cyclo-condensed with L-cysteine to prepare thiazolidine derivative:2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid(GlcNAcCys).The stability of GlcNAcCys was evaluated by high performance liquid chromatography(HPLC)measurement.The results showed that GlcNAcCys Was more stable than other TCA derivatives,especially in alkaline condition.The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation(LPO)in mitochondria and nuclei and.OH-induced LPO in red blood cell (RBC)ghosts models.UV radiation caused dose-dependent LPO in both mitochondria and nuclei,this effect Was catalvzed by addition of Fd2+ while prevented by co-incubation with GlcNAcCys.When nuclei and mitochondria Was treated with 100μl,300μl,500μl of GlcNAcCys and co-incubated at 37℃ for 30min,LPO was decreased to 96%,72%,68%in nuclei and 95%,72%,68% in mitochondria when compared to the UV radiation group respectively.Hydroxyl radicals(.OH)generated by Fenton reaction induced LPO in RBC ghosts.Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde(MDA)formation in antioxidant RBC ghosts.Its inhibition percent Was 14%,35%,36%,42%at 10,20,30,40ms/ml respectively.In a conclusion,the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.

  14. Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Sandra Goetze

    2009-11-01

    Full Text Available Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (XPX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (XPX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species.

  15. Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

    Directory of Open Access Journals (Sweden)

    Michael Eisenhut

    2012-01-01

    Full Text Available Background. Analysis of isoniazid (INH uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2 genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range 2.37 ng/mg (0.76–4.9 versus 1.11 ng/mg (0.02–7.20 (P=0.02. Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7 in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2 in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4 (P<0.05. Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes.

  16. File list: His.NoD.10.Pan_lysine_acetylation.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  3. Aspirin inhibits glucose‑6‑phosphate dehydrogenase activity in HCT 116 cells through acetylation: Identification of aspirin-acetylated sites.

    Science.gov (United States)

    Ai, Guoqiang; Dachineni, Rakesh; Kumar, D Ramesh; Alfonso, Lloyd F; Marimuthu, Srinivasan; Bhat, G Jayarama

    2016-08-01

    Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first reaction in the pentose phosphate pathway, and generates ribose sugars, which are required for nucleic acid synthesis, and nicotinamide adenine dinucleotide phosphate (NADPH), which is important for neutralization of oxidative stress. The expression of G6PD is elevated in several types of tumor, including colon, breast and lung cancer, and has been implicated in cancer cell growth. Our previous study demonstrated that exposure of HCT 116 human colorectal cancer cells to aspirin caused acetylation of G6PD, and this was associated with a decrease in its enzyme activity. In the present study, this observation was expanded to HT‑29 colorectal cancer cells, in order to compare aspirin‑mediated acetylation of G6PD and its activity between HCT 116 and HT‑29 cells. In addition, the present study aimed to determine the acetylation targets of aspirin on recombinant G6PD to provide an insight into the mechanisms of inhibition. The results demonstrated that the extent of G6PD acetylation was significantly higher in HCT 116 cells compared with in HT‑29 cells; accordingly, a greater reduction in G6PD enzyme activity was observed in the HCT 116 cells. Mass spectrometry analysis of aspirin‑acetylated G6PD (isoform a) revealed that aspirin acetylated a total of 14 lysine residues, which were dispersed throughout the length of the G6PD protein. One of the important amino acid targets of aspirin included lysine 235 (K235, in isoform a) and this corresponds to K205 in isoform b, which has previously been identified as being important for catalysis. Acetylation of G6PD at several sites, including K235 (K205 in isoform b), may mediate inhibition of G6PD activity, which may contribute to the ability of aspirin to exert anticancer effects through decreased synthesis of ribose sugars and NADPH.

  4. A reactivity-selectivity study of the Friedel-Crafts acetylation of 3,3′-dimethylbiphenyl and the oxidation of the acetyl derivatives

    Directory of Open Access Journals (Sweden)

    Titinchi Salam JJ

    2012-06-01

    Full Text Available Abstract Background Friedel-Crafts acetylation is an important route to aromatic ketones, in research laboratories and in industry. The acetyl derivatives of 3,3′-dimethylbiphenyl (3,3′-dmbp have applications in the field of liquid crystals and polymers and may be oxidized to the dicarboxylic acids and derivatives that are of interest in cancer treatment. Findings The effect of solvent and temperature on the selectivity of monoacetylation of 3,3’-dmbp by the Perrier addition procedure was studied using stoichiometric amounts of reagents. 4-Ac-3,3′-dmbp was formed almost quantitatively in boiling 1,2-dichloroethane and this is almost twice the yield hitherto reported. Using instead a molar ratio of substrate:AcCl:AlCl3 equal to 1:4:4 or 1:6:6 in boiling 1,2-dichloroethane, acetylation afforded 4,4′- and 4,6′-diacetyl-3,3′-dmbp in a total yield close to 100%. The acetyl derivatives were subsequently converted to the carboxylic acids by hypochlorite oxidation. The relative stabilities of the isomeric products and the corresponding σ-complexes were studied by DFT calculations and the data indicated that mono- and diacetylation followed different mechanisms. Conclusions Friedel-Crafts acetylation of 3,3′-dmbp using the Perrier addition procedure in boiling 1,2-dichloroethane was found to be superior to other recipes. The discrimination against the 6-acetyl derivative during monoacetylation seems to reflect a mechanism including an AcCl:AlCl3 complex or larger agglomerates as the electrophile, whereas the less selective diacetylations of the deactivated 4-Ac-3,3′-dmbp are suggested to include the acetyl cation as the electrophile. The DFT data also showed that complexation of intermediates and products with AlCl3 does not seem to be important in determining the mechanism.

  5. Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.

    Directory of Open Access Journals (Sweden)

    Eri Maria Sol

    Full Text Available Lysine acetylation is a posttranslational modification that is dynamically regulated by the activity of acetyltransferases and deacetylases. The human and mouse genomes encode 18 different lysine deacetylases (KDACs which are key regulators of many cellular processes. Identifying substrates of KDACs and pinpointing the regulated acetylation sites on target proteins may provide important information about the molecular basis of their functions. Here we apply quantitative proteomics to identify endogenous substrates of the mitochondrial deacetylase Sirtuin 3 (Sirt3 by comparing site-specific acetylation in wild-type murine embryonic fibroblasts to Sirt3 knockout cells. We confirm Sirt3-regulated acetylation of several mitochondrial proteins in human cells by comparing acetylation in U2OS cells overexpressing Sirt3 to U2OS cells in which Sirt3 expression was reduced by shRNA. Our data demonstrate that ablation of Sirt3 significantly increases acetylation at dozens of sites on mitochondrial proteins. Substrates of Sirt3 are implicated in various metabolic pathways, including fatty acid metabolism and the tricarboxylic acid cycle. These results imply broader regulatory roles of Sirt3 in the mitochondria by modulating acetylation on diverse substrates. The experimental strategy described here is generic and can be applied to identify endogenous substrates of other lysine deacetylases.

  6. The effects of acetylation on properties of flax fibre and its polypropylene composites

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available Flax fibre was modified with acetylation. The influence of the acetylation on the structure and properties of flax fibre were investigated as well as modified flax fibre reinforced polypropylene composites were also prepared. The catalyst was used to accelerate acetylation reaction rate. Flax fibre was characterised after modification. Surface morphology, moisture absorption property, components content, degree of polymerisation, crystallinity of cellulose and thermal stability of flax fibres were studied. Due to acetylation, the flax fibre surface morphology and moisture resistance properties improved remarkably. Flax fibre (modified and unmodified reinforced polypropylene composites were fabricated with 30 wt% fibre loading. The mechanical properties were investigated for those composites. Tensile and flexural strengths of composites were found to increase with increasing degree of acetylation up to 18% and then decreased. Charpy impact strengths of composites were found to decrease with increasing degree of acetylation. Owing to addition of coupling agent (maleated polypropylene -MAH, the tensile and flexural strength properties were found to increase in between 20 to 35% depending on degree of acetylation.

  7. Histone Acetylation near the Nucleosome Dyad Axis Enhances Nucleosome Disassembly by RSC and SWI/SNF.

    Science.gov (United States)

    Chatterjee, Nilanjana; North, Justin A; Dechassa, Mekonnen Lemma; Manohar, Mridula; Prasad, Rashmi; Luger, Karolin; Ottesen, Jennifer J; Poirier, Michael G; Bartholomew, Blaine

    2015-12-01

    Signaling associated with transcription activation occurs through posttranslational modification of histones and is best exemplified by lysine acetylation. Lysines are acetylated in histone tails and the core domain/lateral surface of histone octamers. While acetylated lysines in histone tails are frequently recognized by other factors referred to as "readers," which promote transcription, the mechanistic role of the modifications in the lateral surface of the histone octamer remains unclear. By using X-ray crystallography, we found that acetylated lysines 115 and 122 in histone H3 are solvent accessible, but in biochemical assays they appear not to interact with the bromodomains of SWI/SNF and RSC to enhance recruitment or nucleosome mobilization, as previously shown for acetylated lysines in H3 histone tails. Instead, we found that acetylation of lysines 115 and 122 increases the predisposition of nucleosomes for disassembly by SWI/SNF and RSC up to 7-fold, independent of bromodomains, and only in conjunction with contiguous nucleosomes. Thus, in combination with SWI/SNF and RSC, acetylation of lateral surface lysines in the histone octamer serves as a crucial regulator of nucleosomal dynamics distinct from the histone code readers and writers.

  8. Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

    Directory of Open Access Journals (Sweden)

    Alicia Lundby

    2012-08-01

    Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

  9. Improved Species-Specific Lysine Acetylation Site Prediction Based on a Large Variety of Features Set.

    Science.gov (United States)

    Wuyun, Qiqige; Zheng, Wei; Zhang, Yanping; Ruan, Jishou; Hu, Gang

    2016-01-01

    Lysine acetylation is a major post-translational modification. It plays a vital role in numerous essential biological processes, such as gene expression and metabolism, and is related to some human diseases. To fully understand the regulatory mechanism of acetylation, identification of acetylation sites is first and most important. However, experimental identification of protein acetylation sites is often time consuming and expensive. Therefore, the alternative computational methods are necessary. Here, we developed a novel tool, KA-predictor, to predict species-specific lysine acetylation sites based on support vector machine (SVM) classifier. We incorporated different types of features and employed an efficient feature selection on each type to form the final optimal feature set for model learning. And our predictor was highly competitive for the majority of species when compared with other methods. Feature contribution analysis indicated that HSE features, which were firstly introduced for lysine acetylation prediction, significantly improved the predictive performance. Particularly, we constructed a high-accurate structure dataset of H.sapiens from PDB to analyze the structural properties around lysine acetylation sites. Our datasets and a user-friendly local tool of KA-predictor can be freely available at http://sourceforge.net/p/ka-predictor. PMID:27183223

  10. Acetylation of Wood Flour from Four Wood Species Grown in Nigeria Using Vinegar and Acetic Anhydride

    Directory of Open Access Journals (Sweden)

    Yakubu Azeh

    2013-01-01

    Full Text Available Effect of acetylation on pretreated wood flour of four different wood species, Boabab (Adansonia digitata, Mahoganny (Daniella oliveri, African locust bean (Parkia biglobosa and Beech wood (Gmelina arborea, had been investigated. The first batch of wood species were acetylated using acetic anhydride while the second batch were acetylated with commercial vinegar. Both experiments were conducted in the presence of varying amount of CaCl2 as catalyst and at temperature of 120°C for 3 h. The success of acetylation was determined based on Weight Percent Gain for each sample treated with either chemicals used. FT-IR, a veritable tool was used for the analysis of both treated and untreated samples to further investigate the success of acetylation. The results showed the presence of important band such as carbonyl absorptions at 1743, 1744, 1746, 1731, 1718 and 1696 cm−1 as appeared separately in the spectra of acetylated samples, confirming esterification occurred. The purpose of this work was to investigate the applicability of vinegar for acetylation of lignocellulosic fibers. Blends/composites were prepared by solution casting and their kinetics investigated in distilled water. The results indicated they could be used in outdoor applications such as, decking and packaging.

  11. Aberrant histone H4 acetylation in dead somatic cell-cloned calves

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Shaohua Wang; Qiang Li; Xiangdong Ding; Yunping Dai; Ning Li

    2008-01-01

    In somatic cell-cloned animals, inefficient epigenetic reprogramming can result in an inappropriate gene expression and histone H4 acetylation is one of the key epigenetic modifications regulating gene expression. In this study, we investigated the levels of histone H4 acetylation of 11 development-related genes and expression levels of 19 genes in lungs of three normal control calves and nine aber-rant somatic cell-cloned calves. The results showed that nine studied genes had decreased acetylation levels in aberrant clones (p 0.05). Whereas 13 genes had significantly decreased expression (p 0.05), and only one gene had higher expression level in clones (p < 0.05). Furthermore, FGFR, GHR, HGFR and IGF1 genes showed lowered levels of both histone H4 acetylation and expression in aberrant clones than in controls, and the level of histone H4 acetylation was even more lowered in aberrant clones than those in controls. It was suggested that the lower levels of histone H4 acetylation in aberrant clones caused by the previous memory of cell differentiation might not support enough chromatin reprogramming, thus affecting appropriate gene expressions, and growth and development of the cloned calves. To our knowledge, this is the first study on how histone H4 acetylation affects gene expression in organs of somatic cell-cloned calves.

  12. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    Science.gov (United States)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  13. Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: overview and application.

    Science.gov (United States)

    Yoshii, Yukie; Furukawa, Takako; Saga, Tsuneo; Fujibayashi, Yasuhisa

    2015-01-28

    Understanding cancer-specific metabolism is important for identifying novel targets for cancer diagnosis and therapy. Induced acetate/acetyl CoA metabolism is a notable feature that is related to fatty acid synthesis supporting tumor growth. In this review, we focused on the recent findings related to cancer acetate/acetyl CoA metabolism. We also introduce [1-¹¹C]acetate positron emission tomography (PET), which is a useful tool to visualize up-regulation of acetate/acetyl CoA metabolism in cancer, and discuss the utility of [1-¹¹C]acetate PET in cancer diagnosis and its application to personalized medicine.

  14. Expression and purification of histone H3 proteins containing multiple sites of lysine acetylation using nonsense suppression.

    Science.gov (United States)

    Young, Isaac A; Mittal, Chitvan; Shogren-Knaak, Michael A

    2016-02-01

    Lysine acetylation is a common post-translational modification, which is especially prevalent in histone proteins in chromatin. A number of strategies exist for generating histone proteins containing lysine acetylation, but an especially attractive approach is to genetically encode acetyl-lysine residues using nonsense suppression. This strategy has been successfully applied to single sites of histone acetylation. However, because histone acetylation can often occur at multiple sites simultaneously, we were interested in determining whether this approach could be extended. Here we show that we can express histone H3 proteins that incorporate up to four sites of lysine acetylation on the histone tail. Because the amount of expressed multi-acetylated histone is reduced relative to the wild type, a purification strategy involving affinity purification and ion exchange chromatography was optimized. This expression and purification strategy ultimately generates H3 histone uniformly acetylated at the desired position at levels and purity sufficient to assemble histone octamers. Histone octamers containing four sites of lysine acetylation were assembled into mononucleosomes and enzymatic assays confirmed that this acetylation largely blocks further acetylation by the yeast SAGA acetyltransferase complex.

  15. An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

    Science.gov (United States)

    Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan

    2015-12-01

    As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

  16. Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation

    DEFF Research Database (Denmark)

    Weinert, Brian T; Wagner, Sebastian A; Horn, Heiko;

    2011-01-01

    . With high-resolution mass spectrometry, we identified 1981 lysine acetylation sites in the proteome of Drosophila melanogaster. We used data sets of experimentally identified acetylation and phosphorylation sites in Drosophila and humans to analyze the evolutionary conservation of these modification...... sites between flies and humans. Site-level conservation analysis revealed that acetylation sites are highly conserved, significantly more so than phosphorylation sites. Furthermore, comparison of lysine conservation in Drosophila and humans with that in nematodes and zebrafish revealed that acetylated...... that acetylation of ubiquitin-conjugating E2 enzymes was evolutionarily conserved, and mutation of a conserved acetylation site impaired the function of the human E2 enzyme UBE2D3. This systems-level analysis of comparative posttranslational modification showed that acetylation is an anciently...

  17. A reactivity-selectivity study of the Friedel-Crafts acetylation of 3,3'-dimethylbiphenyl and the oxidation of the acetyl derivatives

    DEFF Research Database (Denmark)

    Titinchi, Salam J.J.; Kamounah, Fadhil S.; Abbo, Hanna S.;

    2012-01-01

    Background: Friedel-Crafts acetylation is an important route to aromatic ketones, in research laboratories and in industry. The acetyl derivatives of 3,3'-dimethylbiphenyl (3,3'-dmbp) have applications in the field of liquid crystals and polymers and may be oxidized to the dicarboxylic acids and...... converted to the carboxylic acids by hypochlorite oxidation. The relative stabilities of the isomeric products and the corresponding s-complexes were studied by DFT calculations and the data indicated that mono-and diacetylation followed different mechanisms. Conclusions: Friedel-Crafts acetylation of 3...... derivatives that are of interest in cancer treatment. Findings: The effect of solvent and temperature on the selectivity of monoacetylation of 3,3'-dmbp by the Perrier addition procedure was studied using stoichiometric amounts of reagents. 4-Ac-3,3'-dmbp was formed almost quantitatively in boiling 1...

  18. Efficacy of N-acetyl cysteine in traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Katharine Eakin

    Full Text Available In this study, using two different injury models in two different species, we found that early post-injury treatment with N-Acetyl Cysteine (NAC reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting, to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI. For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30-60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man.

  19. Experimental thermochemical study of 3-acetyl-2-methyl-5-phenylthiophene

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro da Silva, Manuel A.V., E-mail: risilva@fc.up.p [Centro de Investigacao em Quimica, Department of Chemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, P-4169-007 Porto (Portugal); Santos, Ana Filipa L.O.M. [Centro de Investigacao em Quimica, Department of Chemistry, Faculty of Science, University of Porto, Rua do Campo Alegre, 687, P-4169-007 Porto (Portugal)

    2010-01-15

    The standard (p{sup 0}=0.1MPa) massic energy of combustion, in oxygen, of the crystalline 3-acetyl-2-methyl-5-phenylthiophene was measured, at T = 298.15 K, by rotating-bomb combustion calorimetry, from which the standard molar enthalpy of formation, in the condensed phase, was calculated as DELTA{sub f}H{sub m}{sup 0}(cr)=-(104.3+-3.1)kJ.mol{sup -1}. The corresponding standard molar enthalpy of sublimation, at T = 298.15 K, DELTA{sub cr}{sup g}H{sub m}{sup 0}=(108.9+-0.4)kJ.mol{sup -1}, was derived by the Clausius-Clapeyron equation, from the temperature dependence of the vapour pressures of this compound, measured by the Knudsen effusion mass-loss technique. From the results presented above, the standard molar enthalpy of formation, in the gaseous phase, at T = 298.15 K, was derived, DELTA{sub f}H{sub m}{sup 0}(g)=(4.6+-3.1)kJ.mol{sup -1}. This value, in conjunction with the literature values of the experimental enthalpies of formation of thiophene, 2-methylthiophene, and 3-acetylthiophene, was used to predict the enthalpic increment due to the introduction of a phenyl group in the position 2- of the thiophene ring. The calculated increment was compared with the corresponding ones in benzene and pyridine derivatives.

  20. Blends of Poly (lactic acid) with Thermoplastic Acetylated Starch

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kun-yu; RAN Xiang-hai; ZHUANG Yu-gang; YAO Bin; DONG Li-song

    2009-01-01

    Blends of poly(lactic acid)(PLA) and thermoplastic acetylated starch(ATPS) were prepared by means of the melt mixing method. The results show that PLA and ATPS were partially miscible, which was confirmed with the measurement of T_g by dynamic mechanical analysis(DMA) and differrential scanning calorimetry(DSC). The mechanical and thermal properties of the blends were improved. With increasing the ATPS content, the elongation at break and impact strength were increased. The elongation at break increased from 5% of neat PLA to 25% of the blend PLA/ATPS40. It was found that the cold crystallization behavior of PLA changed evidently by addition of ATPS. The cold crystallization temperature(T_(cc)) of each of PLA/ATPS blends was found to shift to a lower temperature and the width of exothermic peak became narrow compared with that of neat PLA. The thermogravimetry analy-sis(TGA) results showed that the peak of derivative weight for ATPS moved to higher temperature with increasing PLA content in PLA/ATPS blends. It can be concluded that PLA could increase the thermal stability of ATPS. The rheological measurement reveals the melt elasticity and viscosity of the blends decreased with the increased concentration of ATPS, which was favorable to the processing properties of PLA.

  1. N-acetyl cysteine therapy in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Huseyin Gunduz; Oguz Karabay; Ali Tamer; Resat Ozaras; Ali Mert; Omer Fehmi Tabak

    2003-01-01

    AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P>0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

  2. Reference intervals for acetylated fetal hemoglobin in healthy newborns

    Directory of Open Access Journals (Sweden)

    Renata Paleari

    2014-09-01

    Full Text Available The acetylated fetal hemoglobin (AcHbF derives from an enzyme-mediated post-translational modification occurring on the N-terminal glycine residues of γ-chains. At present, no established data are available on reference intervals for AcHbF in newborns. A total of 92 healthy infants, with gestational age between 37 and 41 weeks were selected for the establishment of AcHbF reference intervals. Blood samples were collected by heel pricking, when collecting routine neonatal screening, and the hemoglobin pattern was analyzed by high-performance liquid chromatography. AcHbF results were then normalized for HbF content in order to account for differences in hemoglobin switch. No difference was found in AcHbF values between genders (P=0.858. AcHbF results were as follow: 12.8±0.8% (mean±standard deviation, reference interval: 11.3-14.3%. This finding could facilitate further studies aimed to assess the possible use of AcHbF, for instance as a possible fetal metabolic biomarker during pregnancy.

  3. Carbohydrate-linked asparagine-101 of prothrombin contains a metal ion protected acetylation site. Acetylation of this site causes loss of metal ion induced protein fluorescence change

    International Nuclear Information System (INIS)

    Prothrombin fragment 1 (prothrombin residues 1-156) contains two acetylation sites that are protected from derivatization by calcium. The first site was protected by only calcium while the second site was protected by magnesium as well. To identify this second acetylation site, fragment 1 was first acetylated with unlabeled reagent in the presence of magnesium. Metal ions were removed, and the protein was acetylated with radiolabeled reagent. The incorporated radiolabel was stable over long periods of time and at acidic or basic pH as long as elevated temperatures were avoided. The radiolabel was removed by treatment of the protein at pH 10 and 50 0C or with 0.2 M hydroxylamine at 50 0C for at least 30 min. Proteolytic degradation of the protein showed that the radioactivity appeared in a tryptic peptide corresponding to residues 94-111 of prothrombin. Amino acid sequence analysis revealed that the radiolabel was associated with an unextracted sequence product. The major radiolabeled product contained Asn101-Ser102 along with the expected chitobiose attached to Asn-101. NMR analysis revealed the presence of three acetate groups which would correspond to two from the chitobiose plus the incorporated acetate residue. Mass spectral analysis showed the correct mass for this glycopeptide plus a single added acetyl group. Amide 1H NMR analysis showed only three amide protons rather than the anticipated four. On the basis of these several observations, it is postulated that the site of acetylation is the β-amide nitrogen of Asn-101. Consequently, these studies showed an unusual chemical reactivity in prothrombin fragment 1. They further show that metal ion binding to prothrombin fragment 1 and subsequent protein fluorescence quenching involve sites ion the kringle region of the protein

  4. Preparation and structural characterization of O-acetyl agarose with low degree of substitution

    Directory of Open Access Journals (Sweden)

    Rosangela B. Garcia

    2000-09-01

    Full Text Available Among the biodegradable polymers, the polysaccharides have been found to be promising carriers for bioactive molecules. From a general standpoint, they present several reactive groups, such as hydroxyl, carboxyl and amine, that can be modified in a number of ways, giving rise to suitable devices for controlled release. In this paper, agarose was submitted to O-acetylation reactions under heterogeneous conditions, using acetic anhydride and pyridine, aiming to observe the effect of acetyl groups on the agarose properties. The products were characterized by Infrared and ¹H NMR spectroscopies. In the range of average acetylation degrees (DA 0.07-0.48, the polymers presented partial solubility in boiling water and in common organic solvents. The ¹H NMR spectra presented evidences of non-homogeneous acetyl group distribution along the chains, as concluded from the solubility of only one of the fractions with DA<0.09, in boiling water .

  5. N-acetyl-L-phenylalanyl-L-phenylalaninol a metabolite of Emericellopsis salmosynnemata.

    Science.gov (United States)

    Argoudelis, A D; Mizsak, S A; Baczynskyj, L

    1975-10-01

    A new metabolite N-acetyl-L-phenylalanyl-L-phenylalaninol was isolated from culture filtrates of Emericellopsis salmosynnemata which produces zervamicins I and II. The structure was assigned from spectral properties and degradative studies. PMID:1184465

  6. Acetylation Enhances the Promoting Role of AIB1 in Breast Cancer Cell Proliferation

    Science.gov (United States)

    You, Dingyun; Zhao, Hongbo; Wang, Yan; Jiao, Yang; Lu, Minnan; Yan, Shan

    2016-01-01

    The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator, which is overexpressed in various types of human cancers, including breast cancer. However, the molecular mechanisms regulating AIB1 function remain largely unknown. In this study, we present evidence demonstrating that AIB1 is acetylated by MOF in human breast cancer cells. Moreover, we also found that the acetylation of AIB1 enhances its function in promoting breast cancer cell proliferation. We further showed that the acetylation of AIB1 is required for its recruitment to E2F1 target genes by E2F1. More importantly, we found that the acetylation levels of AIB1 are greatly elevated in human breast cancer cells compared with that in non-cancerous cells. Collectively, our results shed light on the molecular mechanisms that regulate AIB1 function in breast cancer. PMID:27665502

  7. Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network

    NARCIS (Netherlands)

    Kanski, Regina; Sneeboer, Marjolein A M; van Bodegraven, Emma J; Sluijs, Jacqueline A; Kropff, Wietske; Vermunt, Marit W.; Creyghton, Menno P; De Filippis, Lidia; Vescovi, Angelo; Aronica, Eleonora; van Tijn, P.; van Strien, Miriam E; Hol, Elly M

    2014-01-01

    Glial fibrillary acidic protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation also controls GFAP expression in mature astrocytes. Inhibition of histone deacetylases (HDACs) with trichostati

  8. Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast

    OpenAIRE

    Kagami, Ayano; Sakuno, Takeshi; Yamagishi, Yuya; Ishiguro, Tadashi; Tsukahara, Tatsuya; Shirahige, Katsuhiko; Tanaka, Koichi; Watanabe, Yoshinori

    2011-01-01

    This study shows that multiple acetylations are crucial for establishing and maintaining core centromere cohesion in meiosis. Eso1 establishes it during S phase, whereas Moa1 maintains cohesion after S phase.

  9. Density Functional Theory Study on the Histidine-assisted Mechanism of Arylamine N-Acetyltransferase Acetylation

    Institute of Scientific and Technical Information of China (English)

    QIAO Qing-An; GAO Shan-Min; JIN Yue-Qing; CHEN Xin; SUN Xiao-Min; YANG Chuan-Lu

    2008-01-01

    Arylamine N-acetyltransferases (NATs, EC 2.3.1.5) catalyze the N-acetylation of primary arylamines, and play a key role in the biotransformation and metabolism of drugs, carcinogens, etc.In this paper, three possible reaction mechanisms are investigated and the results indicate that if the acetyl group directly transfers from the donor to the acceptor, the high activation energies will make it hard to obtain the target products.When using histidine to mediate the acetylation process, these energies will drop in the 15~45 kJ/mol range.If the histidine residue is protonated, the corresponding energies will be decreased by about 35~87 kJ/mol.The calculations predict an enzymatic acetylation mechanism that undergoes a thiolate-imidazolium pair, which agrees with the experimental results very well.

  10. The Synthesis of Some Novel N-[a-(Isoflavone-7-O-)Acetyl ] Amino Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel N-[(α)-(isoflavone-7-O-)acetyl] amino acid methyl esters were prepared from the efficient and regioselective alkylation of isoflavones with chloroacetyl amino acid derivatives under mild condition.

  11. Effect of histone acetylate modification on the plasminogen activator inhibitor 1 gene regulation in mesangial cells

    Institute of Scientific and Technical Information of China (English)

    刘念

    2013-01-01

    Objective To investigate the effect of histone acetylation change on the transforming growth factor β1(TGF-β1)-associated plasminogen activator inhibitor 1(PAI-1)regulation in mesangial cells(MCs). Methods MCs were

  12. Catalytic dehalogenation of N-acetyl-L-4-chloro- and N-acetyl-L-4-iodophenylalanine amide in the presence of deuterium

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, J.; Bienert, M.; Niedrich, H.; Zoepfl, H.-J.; Franke, P.

    1986-09-01

    As a model for the tritium labeling of peptides, the catalytic dehalogenation of N-Acetyl-L-4-chloro- and N-Acetyl-L-4-iodo-phenylalanine amide was investigated in the presence of deuterium, using different reaction conditions. A catalyst-mediated transfer of the solvent-hydrogen to the substrate was found to be the most probable reason for the exchange of halogen by hydrogen instead of deuterium. This unwanted transfer was most intensive in the presence of water. An incorporation of additional deuterium besides the 4-position of phenylalanine takes place simultaneously with the dehalogenation especially of the chloro derivative.

  13. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Podbielska, Maria; Dasgupta, Somsankar; Levery, Steven B;

    2010-01-01

    Fast migrating cerebrosides (FMC) are derivatives of galactosylceramide (GalCer). The structures of the most hydrophobic FMC-5, FMC-6, and FMC-7 were determined by electrospray ionization linear ion-trap mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy complementing previous......GL-II from Mycoplasma fermentans. The cross-reactivity of highly acetylated GalCer with microbial acyl-glycolipid raises the possibility that myelin-O-acetyl-cerebrosides, bacterial infection, and neurological disease are linked....

  14. Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors

    OpenAIRE

    Subramanian, Chitra; Opipari, Anthony W.; Bian, Xin; Castle, Valerie P; Kwok, Roland P S

    2005-01-01

    Histone deacetylase inhibitors (HDACIs) are therapeutic drugs that inhibit deacetylase activity, thereby increasing acetylation of many proteins, including histones. HDACIs have antineoplastic effects in preclinical and clinical trials and are being considered for cancers with unmet therapeutic need, including neuroblastoma (NB). Uncertainty of how HDACI-induced protein acetylation leads to cell death, however, makes it difficult to determine which tumors are likely to be responsive to these ...

  15. Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition

    OpenAIRE

    Zhao, Zaorui; Fan, Lu; Fortress, Ashley M.; Boulware, Marissa I.; Frick, Karyn M.

    2012-01-01

    Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol (E2). We first showed that bilateral infusion of ga...

  16. Targeted amino-terminal acetylation of recombinant proteins in E. coli.

    Directory of Open Access Journals (Sweden)

    Matthew Johnson

    Full Text Available One major limitation in the expression of eukaryotic proteins in bacteria is an inability to post-translationally modify the expressed protein. Amino-terminal acetylation is one such modification that can be essential for protein function. By co-expressing the fission yeast NatB complex with the target protein in E.coli, we report a simple and widely applicable method for the expression and purification of functional N-terminally acetylated eukaryotic proteins.

  17. In vitro phosphorylation and acetylation of the murine pocket protein Rb2/p130.

    Directory of Open Access Journals (Sweden)

    Muhammad Saeed

    Full Text Available The retinoblastoma protein (pRb and the related proteins Rb2/p130 and 107 represent the "pocket protein" family of cell cycle regulators. A key function of these proteins is the cell cycle dependent modulation of E2F-regulated genes. The biological activity of these proteins is controlled by acetylation and phosphorylation in a cell cycle dependent manner. In this study we attempted to investigate the interdependence of acetylation and phosphorylation of Rb2/p130 in vitro. After having identified the acetyltransferase p300 among several acetyltransferases to be associated with Rb2/p130 during S-phase in NIH3T3 cells in vivo, we used this enzyme and the CDK4 protein kinase for in vitro modification of a variety of full length Rb2/p130 and truncated versions with mutations in the acetylatable lysine residues 1079, 128 and 130. Mutation of these residues results in the complete loss of Rb2/p130 acetylation. Replacement of lysines by arginines strongly inhibits phosphorylation of Rb2/p130 by CDK4; the inhibitory effect of replacement by glutamines is less pronounced. Preacetylation of Rb2/p130 strongly enhances CDK4-catalyzed phosphorylation, whereas deacetylation completely abolishes in vitro phosphorylation. In contrast, phosphorylation completely inhibits acetylation of Rb2/p130 by p300. These results suggest a mutual interdependence of modifications in a way that acetylation primes Rb2/p130 for phosphorylation and only dephosphorylated Rb2/p130 can be subject to acetylation. Human papillomavirus 16-E7 protein, which increases acetylation of Rb2/p130 by p300 strongly reduces phosphorylation of this protein by CDK4. This suggests that the balance between phosphorylation and acetylation of Rb2/p130 is essential for its biological function in cell cycle control.

  18. Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

    OpenAIRE

    Michael Eisenhut; Detlef Thieme; Dagmar Schmid; Sybille Fieseler; Hans Sachs

    2012-01-01

    Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liq...

  19. AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions.

    Science.gov (United States)

    Salminen, Antero; Kauppinen, Anu; Kaarniranta, Kai

    2016-08-01

    AMP-activated protein kinase (AMPK) and its yeast homolog, Snf1, are critical regulators in the maintenance of energy metabolic balance not only stimulating energy production but also inhibiting energy-consuming processes. The AMPK/Snf1 signaling controls energy metabolism by specific phosphorylation of many metabolic enzymes and transcription factors, enhancing or suppressing their functions. The AMPK/Snf1 complexes can be translocated from cytoplasm into nuclei where they are involved in the regulation of transcription. Recent studies have indicated that AMPK/Snf1 activation can control histone acetylation through different mechanisms affecting not only gene transcription but also many other epigenetic functions. For instance, AMPK/Snf1 enzymes can phosphorylate the histone H3S10 (yeast) and H2BS36 (mammalian) sites which activate specific histone acetyltransferases (HAT), consequently enhancing histone acetylation. Moreover, nuclear AMPK can phosphorylate type 2A histone deacetylases (HDAC), e.g. HDAC4 and HDAC5, triggering their export from nuclei thus promoting histone acetylation reactions. AMPK activation can also increase the level of acetyl CoA, e.g. by inhibiting fatty acid and cholesterol syntheses. Acetyl CoA is a substrate for HATs, thus increasing their capacity for histone acetylation. On the other hand, AMPK can stimulate the activity of nicotinamide phosphoribosyltransferase (NAMPT) which increases the level of NAD(+). NAD(+) is a substrate for nuclear sirtuins, especially for SIRT1 and SIRT6, which deacetylate histones and transcription factors, e.g. those regulating ribosome synthesis and circadian clocks. Histone acetylation is an important epigenetic modification which subsequently can affect chromatin remodeling, e.g. via bromodomain proteins. We will review the signaling mechanisms of AMPK/Snf1 in the control of histone acetylation and subsequently clarify their role in the epigenetic regulation of ribosome synthesis and circadian clocks

  20. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Wan Junhu; Chin Y Eugene; Zhang Hongquan; Zhan Jun; Li Shuai; Ma Ji; Xu Weizhi; Liu Chang; Xue Xiaowei; Xie Yuping; Fang Weigang

    2015-01-01

    Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

  1. Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.

    Science.gov (United States)

    Schroeder, Sabrina; Pendl, Tobias; Zimmermann, Andreas; Eisenberg, Tobias; Carmona-Gutierrez, Didac; Ruckenstuhl, Christoph; Mariño, Guillermo; Pietrocola, Federico; Harger, Alexandra; Magnes, Christoph; Sinner, Frank; Pieber, Thomas R; Dengjel, Jörn; Sigrist, Stephan J; Kroemer, Guido; Madeo, Frank

    2014-07-01

    As the major lysosomal degradation pathway, autophagy represents the guardian of cellular homeostasis, removing damaged and potentially harmful material and replenishing energy reserves in conditions of starvation. Given its vast physiological importance, autophagy is crucially involved in the process of aging and associated pathologies. Although the regulation of autophagy strongly depends on nutrient availability, specific metabolites that modulate autophagic responses are poorly described. Recently, we revealed nucleo-cytosolic acetyl-coenzyme A (AcCoA) as a phylogenetically conserved inhibitor of starvation-induced and age-associated autophagy. AcCoA is the sole acetyl-group donor for protein acetylation, explaining why pharmacological or genetic manipulations that modify the concentrations of nucleo-cytosolic AcCoA directly affect the levels of protein acetylation. The acetylation of histones and cytosolic proteins inversely correlates with the rate of autophagy in yeast and mammalian cells, respectively, despite the fact that the routes of de novo AcCoA synthesis differ across phyla. Thus, we propose nucleo-cytosolic AcCoA to act as a conserved metabolic rheostat, linking the cellular metabolic state to the regulation of autophagy via effects on protein acetylation.

  2. Quantitating the specificity and selectivity of Gcn5-mediated acetylation of histone H3.

    Directory of Open Access Journals (Sweden)

    Yin-Ming Kuo

    Full Text Available Lysine acetyltransferases (KATs play a unique role in regulating gene transcription as well as maintaining the epigenetic state of the cell. KATs such as Gcn5 and p300/CBP can modify multiple residues on a single histone; however, order and specificity of acetylation can be altered by factors such as histone chaperones, subunit proteins or external stimulus. While the importance of acetylation is well documented, it has been difficult to quantitatively measure the specificity and selectivity of acetylation at different residues within a histone. In this paper, we demonstrate a label-free quantitative high throughput mass spectrometry-based assay capable of quantitatively monitoring all known acetylation sites of H3 simultaneously. Using this assay, we are able to analyze the steady-state enzyme kinetics of Gcn5, an evolutionarily conserved KAT. In doing so, we measured Gcn5-mediated acetylation at six residues (K14>K9 ≈ K23> K18> K27 ≈ K36 and the catalytic efficiency (k(cat/K(m for K9, K14, K18, and K23 as well as the nonenzymatic acetylation rate. We observed selectivity differences of up to -4 kcal/mol between K14 and K18, the highest and lowest measurable k(cat/K(m. These data provide a first look at quantitating the specificity and selectivity of multiple lysines on a single substrate (H3 by Gcn5.

  3. Dichotomy in the Epigenetic Mark Lysine Acetylation is Critical for the Proliferation of Prostate Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, Ravi [Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Ave, New York, NY 10029 (United States); Philizaire, Marc [Medgar Evers College, City University of New York, 1638 Bedford Ave, 403D, Brooklyn, NY 11225 (United States); Mujtaba, Shiraz, E-mail: smujtaba@mec.cuny.edu [Department of Structural and Chemical Biology, Mount Sinai School of Medicine, 1425 Madison Ave, New York, NY 10029 (United States); Medgar Evers College, City University of New York, 1638 Bedford Ave, 403D, Brooklyn, NY 11225 (United States)

    2015-08-19

    The dynamics of lysine acetylation serve as a major epigenetic mark, which regulates cellular response to inflammation, DNA damage and hormonal changes. Microarray assays reveal changes in gene expression, but cannot predict regulation of a protein function by epigenetic modifications. The present study employs computational tools to inclusively analyze microarray data to understand the potential role of acetylation during development of androgen-independent PCa. The data revealed that the androgen receptor interacts with 333 proteins, out of which at least 92 proteins were acetylated. Notably, the number of cellular proteins undergoing acetylation in the androgen-dependent PCa was more as compared to the androgen-independent PCa. Specifically, the 32 lysine-acetylated proteins in the cellular models of androgen-dependent PCa were mainly involved in regulating stability as well as pre- and post-processing of mRNA. Collectively, the data demonstrate that protein lysine acetylation plays a crucial role during the transition of androgen-dependent to -independent PCa, which importantly, could also serve as a functional axis to unravel new therapeutic targets.

  4. Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation.

    Directory of Open Access Journals (Sweden)

    Todd J Cohen

    Full Text Available Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer's disease (AD. Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies.

  5. The effect of N-acetyl cysteine on laryngopharyngeal reflux.

    Directory of Open Access Journals (Sweden)

    Payman Dabirmoghaddam

    2013-11-01

    Full Text Available Laryngopharyngeal reflux (LPR is a variant of gastroesophageal reflux disease (GERD in which the stomach contents go up into the pharynx and then down into the larynx. LPR causes a wide spectrum of manifestations mainly related to the upper and the lower respiratory system such as laryngitis, asthma, chronic obstructive pulmonary disease, cough, hoarseness, postnasal drip disease, sinusitis, otitis media, recurrent pneumonia, laryngeal cancer and etc. The object of this study was to examine the effect of N-acetyl Cysteine (NAC with and without Omeprazole on laryngitis and LPR. Ninety patients with laryngitis or its symptoms were referred and randomly assigned into three groups. The first group was treated by Omeprazole and NAC. The second group was treated by Omeprazole and placebo and the last group was treated by NAC and placebo. Duration of treatment was 3 months and all patients were evaluated at the beginning of study, one month and three month after treatment of sign and symptoms, based on reflux symptom index (RSI and reflex finding score (RFS. Based on the results of this study, despite therapeutic efficacy of all treatment protocols, the RSI before and after 3 months treatment had significant difference in (NAS+ Omeprazole and (Omeprazole+ placebo group (P<0.001 in the first group, P<0.001 in the second group and P=0.35 in the third group. Whereas RFS before and after 3 month treatment had significant difference in all groups. (P<0.001 in each group in comparison with itself but this results had not significant difference after 1 month treatment. Our results showed that the combination therapy with Omeprazole and NAC treatment had the most effect on both subjective and objective questionnaire at least after 3 months treatment. Based on the results of the present study, it seems that the use objective tools are more accurate than subjective tools in evaluation of therapeutic effects in patients with GERD-related laryngitis.

  6. Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica.

    Science.gov (United States)

    Xiaojun, Wang; Yan, Liu; Hong, Xu; Xianghong, Zhang; Shifeng, Li; Dingjie, Xu; Xuemin, Gao; Lijuan, Zhang; Bonan, Zhang; Zhongqiu, Wei; Ruimin, Wang; Brann, Darrell; Fang, Yang

    2016-08-31

    Silicosis is the most serious occupational disease in China. The objective of this study was to screen various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) using proteomic profile analysis. We also aimed to explore a potential mechanism of acetylated α-tubulin (α-Ac-Tub) regulation by Ac-SDKP. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to assess the different protein expression profiles between control and silicosis rats treated with or without Ac-SDKP. Twenty-nine proteins were identified to be potentially involved in the progression of silicosis and the anti-fibrotic effect of Ac-SDKP. Our current study finds that 1) the lost expression of Ac-Tub-α may be a new mechanism in rat silicosis; 2) treatment of silicotic rats with N-acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits myofibroblast differentiation and collagen deposition accompanied by stabilizing the expression of α-Ac-Tub in vivo and in vitro, which is related with deacetylase family member 6 (HDAC6) and α-tubulin acetyl transferase (α-TAT1). Our data suggest that α-Ac-Tub regulation by Ac-SDKP may potentially be a new anti-fibrosis mechanism.

  7. Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica

    Science.gov (United States)

    Xiaojun, Wang; Yan, Liu; Hong, Xu; Xianghong, Zhang; Shifeng, Li; Dingjie, Xu; Xuemin, Gao; Lijuan, Zhang; Bonan, Zhang; Zhongqiu, Wei; Ruimin, Wang; Brann, Darrell; Fang, Yang

    2016-01-01

    Silicosis is the most serious occupational disease in China. The objective of this study was to screen various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) using proteomic profile analysis. We also aimed to explore a potential mechanism of acetylated α-tubulin (α-Ac-Tub) regulation by Ac-SDKP. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to assess the different protein expression profiles between control and silicosis rats treated with or without Ac-SDKP. Twenty-nine proteins were identified to be potentially involved in the progression of silicosis and the anti-fibrotic effect of Ac-SDKP. Our current study finds that 1) the lost expression of Ac-Tub-α may be a new mechanism in rat silicosis; 2) treatment of silicotic rats with N-acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits myofibroblast differentiation and collagen deposition accompanied by stabilizing the expression of α-Ac-Tub in vivo and in vitro, which is related with deacetylase family member 6 (HDAC6) and α-tubulin acetyl transferase (α-TAT1). Our data suggest that α-Ac-Tub regulation by Ac-SDKP may potentially be a new anti-fibrosis mechanism. PMID:27577858

  8. PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.

    Directory of Open Access Journals (Sweden)

    Soledad A Camolotto

    Full Text Available BACKGROUND: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression. Despite several transcription factors having been implicated as key regulators of PSG gene family expression; the role of protein acetylation has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: Here, we explored the role of acetylation on PSG gene expression in the human placental-derived JEG-3 cell line. Pharmacological inhibition of histone deacetylases (HDACs up-regulated PSG protein and mRNA expression levels, and augmented the amount of acetylated histone H3 associated with PSG 5'regulatory regions. Moreover, PSG5 promoter activation mediated by Sp1 and KLF6, via the core promoter element motif (CPE, -147/-140, was markedly enhanced in the presence of the HDAC inhibitor trichostatin A (TSA. This effect correlated with an increase in Sp1 acetylation and KLF6 nuclear localization as revealed by immunoprecipitation and subcellular fractionation assays. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetylase (HAT function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. CONCLUSIONS/SIGNIFICANCE: Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization.

  9. Effect of acetylation on antioxidant and cytoprotective activity of polysaccharides isolated from pumpkin (Cucurbita pepo, lady godiva).

    Science.gov (United States)

    Song, Yi; Yang, Yang; Zhang, Yuyu; Duan, Liusheng; Zhou, Chunli; Ni, Yuanying; Liao, Xiaojun; Li, Quanhong; Hu, Xiaosong

    2013-10-15

    Acetylation of pumpkin (Cucurbita pepo, lady godiva variety) polysaccharide using acetic anhydride with pyridines as catalyst under different conditions was conducted to obtain different degrees of acetylation on a laboratory scale. Furthermore, antioxidant activities and cytoprotective effects of pumpkin polysaccharide and its acetylated derivatives were investigated employing various established in vitro systems. Results showed that addition of pyridine as catalyst could increase the degree of substitution, whereas volume of acetic anhydride had little effect. The acetylated polysaccharides in DPPH scavenging radical activity assay, superoxide anion radical activity assay and reducing power assay exhibited higher antioxidant activity than that of unmodified polysaccharide. H2O2-induced oxidative damages on rat thymic lymphocyte were also prevented by pumpkin polysaccharide and its acetylated derivatives and the derivatives presented higher protective effects. On the whole, acetylated polysaccharide showed relevant antioxidant activity both in vitro and in a cell system. PMID:23987399

  10. Behavioral Neuroadaptation to Alcohol: From Glucocorticoids to Histone Acetylation

    Science.gov (United States)

    Mons, Nicole; Beracochea, Daniel

    2016-01-01

    neuroadaptive changes during withdrawal from chronic alcohol intake. It then highlights the role of cAMP–PKA–CREB signaling cascade and histone acetylation within the PFC and limbic structures in alcohol-induced anxiety and behavioral impairments, and how an understanding of functional alterations of these pathways might lead to better treatments for neuropsychiatric disorders. PMID:27766083

  11. N-acetyl-L-tyrosine (NAT) as a substrate for mushroom tyrosinase.

    Science.gov (United States)

    Kahn, V; Ben-Shalom, N

    1998-02-01

    N-acetyl tyrosine (NAT) is hydroxylated by mushroom tyrosinase and the N-acetyl dopa formed is oxidized by the enzyme to N-acetyl dopaquinone (lambda max = 390 +/- 10 nm). H2O2 and NH2OH each shortened the lag period of NAT hydroxylation by the enzyme. H2O2 had an effect on the changes with time in the spectrum of product(s) formed and on the spectrum of the final product(s) obtained when NAT was hydroxylated by mushroom tyrosinase, in a manner suggesting that H2O2 converts N-acetyl dopaquinone to a pink-violet product(s) (lambda max = 490 nm), whereas such a product(s) was not formed in the absence of H2O2. A pink-violet product(s) (lambda max 490 +/- 20 nm) was also formed when NAT was hydroxylated by mushroom tyrosinase in the presence of NH2OH or para amino benzoic acid (PABA), probably as a result of an interaction between N-acetyl dopaquinone and NH2OH or PABA forming mono- or di-oximes. Kojic acid (5-hydroxy-2-hydroxymethyl)-4H-pyran-4-one) inhibited effectively the rate of NAT hydroxylation by mushroom tyrosinase in the absence or presence of H2O2. When NAT was oxidized by the enzyme in the absence of kojic acid, N-acetyl dopaquinone was formed at once and a shoulder at 490-530 nm appeared later. Under identical conditions but in the presence of kojic acid, a yellow product(s), characterized by a peak at 320 +/- 10 nm, was detected, suggesting that N-acetyl dopaquinone oxidizes kojic acid to the yellow product(s). Maltol (3-hydroxy-2-methyl-4H-pyran-4-one), a gamma-pyrone derivative structurally related to kojic acid, also inhibited the rate of NAT hydroxylation by mushroom tyrosinase. The addition of maltol at the plateau phase of the reaction resulted in an immediate decline in absorbance at 400 nm, suggesting that maltol conjugates with N-acetyl dopaquinone, yielding a product(s) characterized by a lower extinction coefficient at 400 nm than that of N-acetyl dopaquinone alone. The final brown-red product(s) formed when NAT was hydroxylated by mushroom

  12. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  13. Acetyl hexapeptide-3 in a cosmetic formulation acts on skin mechanical properties - clinical study

    Directory of Open Access Journals (Sweden)

    Kassandra Azevedo Tadini

    2015-12-01

    Full Text Available abstract Acetyl hexapeptide-3 has been used in anti-aging topical formulations aimed at improving skin appearance. However, few basic studies address its effects on epidermis and dermis, when vehiculated in topical formulations. Thus, the objective of this study was to determine the clinical efficacy of acetyl hexapeptide-3 using biophysical techniques. For this purpose, formulations with and without acetyl hexapeptide-3 were applied to the ventral forearm and the face area of forty female volunteers. Skin conditions were evaluated after 2 and 4-week long daily applications, by analyzing the stratum corneum water content and the skin mechanical properties, using three instruments, the Corneometer(r CM 825, CutometerSEM 575 and ReviscometerRV600. All formulations tested increased the stratum corneum water content in the face region, which remained constant until the end of the study. In contrast, only formulations containing acetyl hexapeptide-3 exhibit a significant effect on mechanical properties, by decreasing the anisotropy of the face skin. No significant effects were observed in viscoelasticity parameters. In conclusion, the effects of acetyl hexapeptide-3 on the anisotropy of face skin characterize the compound as an effective ingredient for improving conditions of the cutaneous tissue, when used in anti-aging cosmetic formulations.

  14. Histone H4 lysine 20 acetylation is associated with gene repression in human cells.

    Science.gov (United States)

    Kaimori, Jun-Ya; Maehara, Kazumitsu; Hayashi-Takanaka, Yoko; Harada, Akihito; Fukuda, Masafumi; Yamamoto, Satoko; Ichimaru, Naotsugu; Umehara, Takashi; Yokoyama, Shigeyuki; Matsuda, Ryo; Ikura, Tsuyoshi; Nagao, Koji; Obuse, Chikashi; Nozaki, Naohito; Takahara, Shiro; Takao, Toshifumi; Ohkawa, Yasuyuki; Kimura, Hiroshi; Isaka, Yoshitaka

    2016-01-01

    Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression. PMID:27064113

  15. Solvent-free acetylation of cellulose nanofibers for improving compatibility and dispersion.

    Science.gov (United States)

    Ashori, Alireza; Babaee, Mehran; Jonoobi, Mehdi; Hamzeh, Yahya

    2014-02-15

    Cellulose nanofibers (CNFs), as bio-materials derived from wood or non-wood plants, have the advantages of being biodegradable, renewable, low cost, and having good mechanical properties compared to synthetic nanofibers. CNFs have been used as reinforcement in polymeric matrices, however, due to their polar surface, their dispersibility in non-polar solvents and compatibility with hydrophobic matrices are poor. In this work, the chemical modification of CNFs, using acetic anhydride in the presence of pyridine as a catalyst, was studied with the aim of changing the surface properties. Native and chemically modified CNFs were characterized in terms of dynamic absorption, thermal stability, surface chemistry, morphology, and crystal structure. The reaction of acetylation between the acetyl groups and the hydroxyl groups of the CNFs was examined using Fourier transform infrared (FT-IR) analysis, while its extent was assessed by titration. The ester content of CNFs was higher for the acetylated samples compared to the control samples. It was also shown that the crystallinity decreased moderately as a result of esterification. Thermal stability of the modified nanofibers was slightly increased. Unlike native CNFs, a stable aqueous suspension was obtained with the modified nanofibers in both ethanol and acetone. The contact angle measurements confirmed that the surface characteristics of acetylated CNFs were changed from hydrophilic to more hydrophobic. In addition, the obtained acetylated CNFs showed more hydrophobic surface, which is in favor of enhancing the hydrophobic non-polar mediums. PMID:24507293

  16. The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation

    Energy Technology Data Exchange (ETDEWEB)

    Coutinho Carneiro, Vitor; Moraes Maciel, Renata de; Caetano de Abreu da Silva, Isabel; Furtado Madeira da Costa, Rodrigo [Instituto de Bioquimica Medica, Programa de Biotecnologia e Biologia Molecular, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil); Neto Paiva, Claudia; Torres Bozza, Marcelo [Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Goes, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil); Rosado Fantappie, Marcelo, E-mail: fantappie@bioqmed.ufrj.br [Instituto de Bioquimica Medica, Programa de Biotecnologia e Biologia Molecular, Universidade Federal do Rio de Janeiro, CCS, Ilha do Fundao, Rio de Janeiro 21941-590 (Brazil)

    2009-12-25

    Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1{Delta}C) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1{Delta}C were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.

  17. Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

    Science.gov (United States)

    Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

    1988-01-01

    Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

  18. Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract

    Science.gov (United States)

    Rong, Xianfang; Qiu, Xiaodi; Jiang, Yongxiang; Li, Dan; Xu, Jie; Zhang, Yinglei; Lu, Yi

    2016-01-01

    Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types—nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)—using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at −600 bp of the SOD1 promoter of cataract lenses, and hypoacetylated at −1500, −1200, and −900 bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA’s effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts. PMID:27703255

  19. The Caenorhabditis elegans Elongator complex regulates neuronal alpha-tubulin acetylation.

    Directory of Open Access Journals (Sweden)

    Jachen A Solinger

    2010-01-01

    Full Text Available Although acetylated alpha-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate alpha-tubulin acetylation are, to date, largely unknown. Therefore, a genetic screen was employed in the nematode Caenorhabditis elegans that identified the Elongator complex as a possible regulator of alpha-tubulin acetylation. Detailed characterization of mutant animals revealed that the acetyltransferase activity of the Elongator is indeed required for correct acetylation of microtubules and for neuronal development. Moreover, the velocity of vesicles on microtubules was affected by mutations in Elongator. Elongator mutants also displayed defects in neurotransmitter levels. Furthermore, acetylation of alpha-tubulin was shown to act as a novel signal for the fine-tuning of microtubules dynamics by modulating alpha-tubulin turnover, which in turn affected neuronal shape. Given that mutations in the acetyltransferase subunit of the Elongator (Elp3 and in a scaffold subunit (Elp1 have previously been linked to human neurodegenerative diseases, namely Amyotrophic Lateral Sclerosis and Familial Dysautonomia respectively highlights the importance of this work and offers new insights to understand their etiology.

  20. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    International Nuclear Information System (INIS)

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs

  1. Ach1 is involved in shuttling mitochondrial acetyl units for cytosolic C2 provision in Saccharomyces cerevisiae lacking pyruvate decarboxylase

    DEFF Research Database (Denmark)

    Chen, Yun; Zhang, Yiming; Siewers, Verena;

    2015-01-01

    Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast Saccha...... mitochondria and the cytosol. These results will increase our fundamental understanding of intracellular transport of acetyl units, and also help to develop microbial cell factories for many kinds of acetyl-CoA derived products.......Acetyl-coenzyme A (acetyl-CoA) is not only an essential intermediate in central carbon metabolism, but also an important precursor metabolite for native or engineered pathways that can produce many products of commercial interest such as pharmaceuticals, chemicals or biofuels. In the yeast......-fermentative yeast strain. We found that mitochondrial Ach1 can convert acetyl-CoA in this compartment into acetate, which crosses the mitochondrial membrane before being converted into acetyl-CoA in the cytosol. Based on our finding we propose a model in which acetate can be used to exchange acetyl units between...

  2. N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Gabriella M A Forte

    2011-05-01

    Full Text Available Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%-80% of proteins reportedly altered in this way. Here we report a systematic analysis of the predicted N-terminal processing of cytosolic proteins versus those destined to be sorted to the secretory pathway. While cytosolic proteins were profoundly biased in favour of processing, we found an equal and opposite bias against such modification for secretory proteins. Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery. Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species.

  3. Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.

    Science.gov (United States)

    Nguyen, T Van; Lee, J Eugene; Sweredoski, Michael J; Yang, Seung-Joo; Jeon, Seung-Je; Harrison, Joseph S; Yim, Jung-Hyuk; Lee, Sang Ghil; Handa, Hiroshi; Kuhlman, Brian; Jeong, Ji-Seon; Reitsma, Justin M; Park, Chul-Seung; Hess, Sonja; Deshaies, Raymond J

    2016-03-17

    Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4(CRBN) that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.

  4. Hydrolysis of Wheat Arabinoxylan by Two Acetyl Xylan Esterases from Chaetomium thermophilum

    DEFF Research Database (Denmark)

    Tong, Xiaoxue; Lange, Lene; Grell, Morten Nedergaard;

    2015-01-01

    The thermophilic filamentous ascomycete Chaetomium thermophilum produces functionally diverse hemicellulases when grown on hemicellulose as carbon source. Acetyl xylan esterase (EC 3.1.1.72) is an important accessory enzyme in hemicellulose biodegradation. Although the genome of C. thermophilum has...... been sequenced, its carbohydrate esterases are not annotated yet. We applied peptide pattern recognition (PPR) tool for sequence analysis of the C. thermophilum genome, and 11 carbohydrate esterase genes were discovered. Furthermore, we cloned and heterologously expressed two putative acetyl xylan...... esterase genes, CtAxeA and CtAxeB, in Pichia pastoris. The recombinant proteins, rCtAxeA and rCtAxeB, released acetic acids from p-nitrophenyl acetate and water-insoluble wheat arabinoxylan. These results indicate that CtAxeA and CtAxeB are true acetyl xylan esterases. For both recombinant esterases, over...

  5. 2-acetyl-1-pyrroline - key aroma compound in Mediterranean dried sausages

    DEFF Research Database (Denmark)

    Stahnke, Marie Louise Heller

    2000-01-01

    In a study characterising sausage types from various parts of Europe, ten Mediterranean and Northern European fermented, dried sausages were compared using static headspace gas chromatography-olfactometry and a sniffing panel of five members. The greatest difference between the Northern...... and Southern types were attributed to a burned coffee odour from smoke in the smoked sausages and a popcorn note in the Mediterranean products covered with mould. The two compounds were 2-furfurylthiol and 2-acetyl-1-pyrroline, respectively. An analysis of five dried, moulded sausages showed that the surface...... edge of the sausages contained higher amounts of 2-acetyl-1-pyrroline than the core, indicating that the mould growing on the surface of Mediterranean products produces 2-acetyl-1-pyrroline....

  6. Preparation of Acetylated Guar Gum – Unsaturated Polyester Composites & Effect of Water on Their Properties

    Directory of Open Access Journals (Sweden)

    David D’Melo

    2012-07-01

    Full Text Available Guar gum has seen extensive use in blends, however, its application as a filler in thermoset composites has as yet not been investigated. The effect of the addition of guar gum and its acetyl derivatives on the kinetics of water diffusion in unsaturated polyester composites was studied. The effect of water on the mechanical properties of the composites was studied with respect to the nature of filler, filler concentration and time of immersion. All the mechanical properties were observed to decrease on exposure to water. Further, it was observed that acetylated guar gum, with a degree of substitution of 0.21, showed the best mechanical properties, surpassing the other filled composites and that of the pure unsaturated polyester. Thus, acetylated guar gum showed promise as eco-friendly filler in composite formulation.

  7. GCN5-dependent acetylation of HIV-1 integrase enhances viral integration

    Directory of Open Access Journals (Sweden)

    Albanese Alberto

    2010-03-01

    Full Text Available Abstract Background An essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase (IN, the enzyme that catalyzes the integration reaction, is positively regulated by acetylation mediated by the histone acetyltransferase (HAT p300. Results In this study we demonstrate that another cellular HAT, GCN5, acetylates IN leading to enhanced 3'-end processing and strand transfer activities. GCN5 participates in the integration step of HIV-1 replication cycle as demonstrated by the reduced infectivity, due to inefficient provirus formation, in GCN5 knockdown cells. Within the C-terminal domain of IN, four lysines (K258, K264, K266, and K273 are targeted by GCN5 acetylation, three of which (K264, K266, and K273 are also modified by p300. Replication analysis of HIV-1 clones carrying substitutions at the IN lysines acetylated by both GCN5 and p300, or exclusively by GCN5, demonstrated that these residues are required for efficient viral integration. In addition, a comparative analysis of the replication efficiencies of the IN triple- and quadruple-mutant viruses revealed that even though the lysines targeted by both GCN5 and p300 are required for efficient virus integration, the residue exclusively modified by GCN5 (K258 does not affect this process. Conclusions The results presented here further demonstrate the relevance of IN post-translational modification by acetylation, which results from the catalytic activities of multiple HATs during the viral replication cycle. Finally, this study contributes to clarifying the recent debate raised on the role of IN acetylated lysines during HIV-1 infection.

  8. Chromosomal protein HMGN1 enhances the acetylation of lysine 14 in histone H3

    OpenAIRE

    Lim, Jae-Hwan; West, Katherine L.; Rubinstein, Yaffa; Bergel, Michael; Postnikov, Yuri V.; Bustin, Michael

    2005-01-01

    The acetylation levels of lysine residues in nucleosomes, which are determined by the opposing activities of histone acetyltransferases (HATs) and deacetylases, play an important role in regulating chromatin-related processes, including transcription. We report that HMGN1, a nucleosomal binding protein that reduces the compaction of the chromatin fiber, increases the levels of acetylation of K14 in H3. The levels of H3K14ac in Hmgn1−/− cells are lower than in Hmgn1+/+ cells. Induced expressio...

  9. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

    Science.gov (United States)

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification.

  10. Inhibition effects of acetyl coumarines and thiazole derivatives on corrosion of zinc in acidic medium

    Indian Academy of Sciences (India)

    A V Shanbhag; T V Venkatesha; R A Prabhu; B M Praveen

    2011-06-01

    The corrosion inhibition characteristics of acetyl coumarine (AC), bromo acetyl coumarine (BAC) and thiazole derivatives (BTMQ and BTCQ) on the corrosion of zinc in 0.1 M HCl solution were investigated by weight loss, potentiodynamic polarization and impedance techniques. The inhibition efficiency increased with increase in inhibitor concentration upto 5 × 10-4 M, then gave almost same inhibition efficiency. The polarizationmeasurements indicated the mixed nature of inhibitors. The adsorption of compounds obeyed Langmuir’s adsorption isotherm. The thermodynamic functions for adsorption processes were evaluated.

  11. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation

    DEFF Research Database (Denmark)

    Lombard, David B; Alt, Frederick W; Cheng, Hwei-Ling;

    2007-01-01

    Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies of the sirtuin SIRT3 have so far been limited to cell culture systems. Here, we investigate the localization and function of SIRT3 in vivo. We show that endogenous mouse SIRT3 is a soluble......, a process previously suggested to involve SIRT3. Overall, our results extend the recent finding of lysine acetylation of mitochondrial proteins and demonstrate that SIRT3 has evolved to control reversible lysine acetylation in this organelle....

  12. Hydrolysis of wheat B-starch and characterisation of acetylated maltodextrin.

    Science.gov (United States)

    Smrčková, Petra; Horský, Jiří; Šárka, Evžen; Koláček, Jaroslav; Netopilík, Miloš; Walterová, Zuzana; Kruliš, Zdeněk; Synytsya, Andrey; Hrušková, Kateřina

    2013-10-15

    Wheat B-starch was hydrolysed by α-amylase "Liquozyme supra" from Bacillus licheniformis at 90 °C and pH 7. After 2 h, the dextrose equivalent was 18; according to size exclusion chromatography, however, the hydrolysate contained not only dominant malto-oligosaccharides with the degree of polymerisation (DP)40. This non-uniformity of acetylated maltodextrin, both with respect to DP and to DS, must be taken into account in the development of acetylated-maltodextrin applications such as use as plasticisers or compatibilisers in biodegradable composites.

  13. Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

    DEFF Research Database (Denmark)

    Bennetzen, Martin; Andersen, J.S.; Lasen, D.H.;

    2013-01-01

    Genotoxic insults, such as ionizing radiation (IR), cause DNA damage that evokes a multifaceted cellular DNA damage response (DDR). DNA damage signaling events that control protein activity, subcellular localization, DNA binding, protein-protein interactions, etc. rely heavily on time...... to assess lysine acetylation status and thereby validate the mass spectrometry data. We thus present evidence that nuclear proteins, including those known to regulate cellular functions via epigenetic modifications of histones, are regulated by (de)acetylation in a timely manner upon cell's exposure...

  14. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Science.gov (United States)

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications.

  15. Histone H3 lysine 56 acetylation and the response to DNA replication fork damage

    DEFF Research Database (Denmark)

    Wurtele, Hugo; Kaiser, Gitte Schalck; Bacal, Julien;

    2012-01-01

    In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA...... damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin...

  16. On the path to glycan conformer identification: Gas-phase study of the anomers of methyl glycosides of N-acetyl-d-glucosamine and N-acetyl-d-galactosamine

    NARCIS (Netherlands)

    Contreras, C. S.; Polfer, N. C.; Oomens, J.; Steill, J. D.; Bendiak, B.; Eyler, J. R.

    2012-01-01

    The methyl glycosides of N-acetyl-d-glucosamine (d-GlcNAc) and N-acetyl-d-galactosamine (d-GalNAc) have been used as model glycan analogs to study the effects of lithium cation binding on glycan structure in gas-phase experiments. Infrared multiple photon dissociation (IRMPD) spectra for the two Li+

  17. On the path to glycan conformer identification: Gas-phase study of the anomers of methyl glycosides of N-acetyl-D-glucosamine and N-acetyl-D-galactosamine

    NARCIS (Netherlands)

    C.S. Contreras; N.C. Polfer; J. Oomens; J.D. Steill; B. Bendiak; J.R. Eyler

    2012-01-01

    The methyl glycosides of N-acetyl-d-glucosamine (d-GlcNAc) and N-acetyl-d-galactosamine (d-GalNAc) have been used as model glycan analogs to study the effects of lithium cation binding on glycan structure in gas-phase experiments. Infrared multiple photon dissociation (IRMPD) spectra for the two Li+

  18. Reduced Histone H3 Acetylation in CD4+ T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults

    Directory of Open Access Journals (Sweden)

    Xi-yu Liu

    2015-01-01

    Full Text Available Aims. Latent autoimmune diabetes in adults (LADA is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4+ T lymphocytes from LADA patients. Methods. Blood CD4+ T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP and histone deacetylases (HDAC1, HDAC2, and HDAC7 was measured by real-time polymerase chain reaction (RT-PCR. Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients’ CD4+ T lymphocytes (P<0.05. Global level of H4 acetylation was not statistically different. Among LADA, CD4+ T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4+ T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications.

  19. Surface modification of bacterial cellulose nanofibers for property enhancement of optically transparent composites: dependence on acetyl-group DS.

    Science.gov (United States)

    Ifuku, Shinsuke; Nogi, Masaya; Abe, Kentaro; Handa, Keishin; Nakatsubo, Fumiaki; Yano, Hiroyuki

    2007-06-01

    Bacterial cellulose (BC) nanofibers were acetylated to enhance the properties of optically transparent composites of acrylic resin reinforced with the nanofibers. A series of BC nanofibers acetylated from degree-of-substitution (DS) 0 to 1.76 were obtained. X-ray diffraction profiles indicated that acetylation proceeded from the surface to the core of BC nanofibers, and scanning electron microscopy images showed that the volume of nanofibers increases by the bulky acetyl group. Since acetylation decreased the refractive index of cellulose, regular transmittance of composites comprised of 63% BC nanofiber was improved, and deterioration at 580 nm because of fiber reinforcement was suppressed to only 3.4%. Acetylation of nanofibers changed their surface properties and reduced the moisture content of the composite to about one-third that of untreated composite, although excessive acetylation increased hygroscopicity. Furthermore, acetylation was found to reduce the coefficient of thermal expansion of a BC sheet from 3 x 10(-6) to below 1 x 10(-6) 1/K.

  20. High-resolution 1H-NMR spectroscopy of free and glycosidically linked O-acetylated sialic acids

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Haverkamp, J.; Halbeek, H. van; Dorland, L.; Pfeil, R.; Schauer, R.

    1982-01-01

    A number of naturally occurring and synthetic, partially O-acetylated derivatives of N-acetylneuraminic and N-glycoloylneuraminic acids have been investigated by 360-MHz 1H-NMR spectroscopy. O-Acetylation causes strong downfield shifts for the resonances of neighbouring sugar-skeleton protons. The c

  1. 40 CFR 180.1089 - Poly-N-acetyl-D-glucosamine; exemption from the requirement of tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Poly-N-acetyl-D-glucosamine; exemption from the requirement of tolerance. 180.1089 Section 180.1089 Protection of Environment ENVIRONMENTAL... biochemical nematicide poly-N-acetyl-D-glucosamine on a variety of agricultural crops....

  2. Engineering Acetyl Coenzyme A Supply: Functional Expression of a Bacterial Pyruvate Dehydrogenase Complex in the Cytosol of Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Kozak, B.U.; Van Rossum, H.M.; Luttik, M.A.H.; Akeroyd, M.; Benjamin, K.R.; Wu, L.; De Vries, S.; Daran, J.M.; Pronk, J.T.; Van Maris, A.J.A.

    2014-01-01

    The energetic (ATP) cost of biochemical pathways critically determines the maximum yield of metabolites of vital or commercial relevance. Cytosolic acetyl coenzyme A (acetyl-CoA) is a key precursor for biosynthesis in eukaryotes and for many industrially relevant product pathways that have been intr

  3. Engineering acetyl coenzyme A supply: functional expression of a bacterial pyruvate dehydrogenase complex in the cytosol of Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Kozak, B.U.; Van Rossum, M.H.; Luttik, M.A.; Akeroyd, M.; Benjamin, K.R.; Wu, L.; De Vries, S.; Daran, J.M.; Pronk, J.T.; Van Maris, A.J.A.

    2014-01-01

    The energetic (ATP) cost of biochemical pathways critically determines the maximum yield of metabolites of vital or commercial relevance. Cytosolic acetyl coenzyme A (acetyl-CoA) is a key precursor for biosynthesis in eukaryotes and for many industrially relevant product pathways that have been intr

  4. Quantitative Measurement of Histone Tail Acetylation Reveals Stage-Specific Regulation and Response to Environmental Changes during Drosophila Development.

    Science.gov (United States)

    Henry, Ryan A; Singh, Tanu; Kuo, Yin-Ming; Biester, Alison; O'Keefe, Abigail; Lee, Sandy; Andrews, Andrew J; O'Reilly, Alana M

    2016-03-22

    Histone modification plays a major role in regulating gene transcription and ensuring the healthy development of an organism. Numerous studies have suggested that histones are dynamically modified during developmental events to control gene expression levels in a temporal and spatial manner. However, the study of histone acetylation dynamics using currently available techniques is hindered by the difficulty of simultaneously measuring acetylation of the numerous potential sites of modification present in histones. Here, we present a methodology that allows us to combine mass spectrometry-based histone analysis with Drosophila developmental genetics. Using this system, we characterized histone acetylation patterns during multiple developmental stages of the fly. Additionally, we utilized this analysis to characterize how treatments with pharmacological agents or environmental changes such as γ-irradiation altered histone acetylation patterns. Strikingly, γ-irradiation dramatically increased the level of acetylation at H3K18, a site linked to DNA repair via nonhomologous end joining. In mutant fly strains deficient in DNA repair proteins, however, this increase in the level of H3K18 acetylation was lost. These results demonstrate the efficacy of our combined mass spectrometry system with a Drosophila model system and provide interesting insight into the changes in histone acetylation during development, as well as the effects of both pharmacological and environmental agents on global histone acetylation.

  5. Inhibition of Different Histone Acetyltransferases (HATs) Uncovers Transcription-Dependent and -Independent Acetylation-Mediated Mechanisms in Memory Formation

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-01-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied…

  6. Exploring the Possible Role of Lysine Acetylation on Entamoeba histolytica Virulence: A Focus on the Dynamics of the Actin Cytoskeleton

    Directory of Open Access Journals (Sweden)

    L. López-Contreras

    2013-01-01

    Full Text Available Cytoskeleton remodeling can be regulated, among other mechanisms, by lysine acetylation. The role of acetylation on cytoskeletal and other proteins of Entamoeba histolytica has been poorly studied. Dynamic rearrangements of the actin cytoskeleton are crucial for amebic motility and capping formation, processes that may be effective means of evading the host immune response. Here we report the possible effect of acetylation on the actin cytoskeleton dynamics and in vivo virulence of E. histolytica. Using western blot, immunoprecipitation, microscopy assays, and in silico analysis, we show results that strongly suggest that the increase in Aspirin-induced cytoplasm proteins acetylation reduced cell movement and capping formation, likely as a consequence of alterations in the structuration of the actin cytoskeleton. Additionally, intrahepatic inoculation of Aspirin-treated trophozoites in hamsters resulted in severe impairment of the amebic virulence. Taken together, these results suggest an important role for lysine acetylation in amebic invasiveness and virulence.

  7. Exploring the possible role of lysine acetylation on Entamoeba histolytica virulence: a focus on the dynamics of the actin cytoskeleton.

    Science.gov (United States)

    López-Contreras, L; Hernández-Ramírez, V I; Lagunes-Guillén, A E; Montaño, Sarita; Chávez-Munguía, B; Sánchez-Ramírez, B; Talamás-Rohana, P

    2013-01-01

    Cytoskeleton remodeling can be regulated, among other mechanisms, by lysine acetylation. The role of acetylation on cytoskeletal and other proteins of Entamoeba histolytica has been poorly studied. Dynamic rearrangements of the actin cytoskeleton are crucial for amebic motility and capping formation, processes that may be effective means of evading the host immune response. Here we report the possible effect of acetylation on the actin cytoskeleton dynamics and in vivo virulence of E. histolytica. Using western blot, immunoprecipitation, microscopy assays, and in silico analysis, we show results that strongly suggest that the increase in Aspirin-induced cytoplasm proteins acetylation reduced cell movement and capping formation, likely as a consequence of alterations in the structuration of the actin cytoskeleton. Additionally, intrahepatic inoculation of Aspirin-treated trophozoites in hamsters resulted in severe impairment of the amebic virulence. Taken together, these results suggest an important role for lysine acetylation in amebic invasiveness and virulence.

  8. Specific synthesis of neurostatin and gangliosides O-acetylated in the outer sialic acids using a sialate transferase.

    Directory of Open Access Journals (Sweden)

    Lorenzo Romero-Ramírez

    Full Text Available Gangliosides are sialic acid containing glycosphingolipids, commonly found on the outer leaflet of the plasma membrane. O-acetylation of sialic acid hydroxyl groups is one of the most common modifications in gangliosides. Studies on the biological activity of O-acetylated gangliosides have been limited by their scarcity in nature. This comparatively small change in ganglioside structure causes major changes in their physiological properties. When the ganglioside GD1b was O-acetylated in the outer sialic acid, it became the potent inhibitor of astroblast and astrocytoma proliferation called Neurostatin. Although various chemical and enzymatic methods to O-acetylate commercial gangliosides have been described, O-acetylation was nonspecific and produced many side-products that reduced the yield. An enzyme with O-acetyltransferase activity (SOAT has been previously cloned from the bacteria Campylobacter jejuni. This enzyme catalyzed the acetylation of oligosaccharide-bound sialic acid, with high specificity for terminal alpha-2,8-linked residues. Using this enzyme and commercial gangliosides as starting material, we have specifically O-acetylated the gangliosides' outer sialic acids, to produce the corresponding gangliosides specifically O-acetylated in the sialic acid bound in alpha-2,3 and alpha-2,8 residues. We demonstrate here that O-acetylation occurred specifically in the C-9 position of the sialic acid. In summary, we present a new method of specific O-acetylation of ganglioside sialic acids that permits the large scale preparation of these modified glycosphingolipids, facilitating both, the study of their mechanism of antitumoral action and their use as therapeutic drugs for treating glioblastoma multiform (GBM patients.

  9. The effect of N-acetyl-L-cysteine on the viscosity of ileal neobladder mucus.

    NARCIS (Netherlands)

    Schrier, B.P.; Lichtendonk, W.J.; Witjes, J.A.

    2002-01-01

    N-acetyl-L-cysteine (NAC) proved to be an effective mucolytic in pulmonary secretions. Our goal was to investigate the in vitro effect of NAC on viscosity of ileal neobladder mucus. The urine of a patient with an ileal neobladder was collected during the first 7 days postoperatively and stored in a

  10. Salmonella typhimurium infection increases p53 acetylation in intestinal epithelial cells.

    Science.gov (United States)

    Wu, Shaoping; Ye, Zhongde; Liu, Xingyin; Zhao, Yun; Xia, Yinglin; Steiner, Andrew; Petrof, Elaine O; Claud, Erika C; Sun, Jun

    2010-05-01

    The ability of Salmonella typhimurium to enter intestinal epithelial cells constitutes a crucial step in pathogenesis. Salmonella invasion of the intestinal epithelium requires bacterial type three secretion system. Type three secretion system is a transport device that injects virulence proteins, called effectors, to paralyze or reprogram the eukaryotic cells. Avirulence factor for Salmonella (AvrA) is a Salmonella effector that inhibits the host's inflammatory responses. The mechanism by which AvrA modulates host cell signaling is not entirely clear. p53 is situated at the crossroads of a network of signaling pathways that are essential for genotoxic and nongenotoxic stress responses. We hypothesized that Salmonella infection activates the p53 pathway. We demonstrated that Salmonella infection increased p53 acetylation. Cells infected with AvrA-sufficient Salmonella have increased p53 acetylation, whereas cells infected with AvrA-deficient Salmonella have less p53 acetylation. In a cell-free system, AvrA possessed acetyltransferase activity and used p53 as a substrate. AvrA expression increased p53 transcriptional activity and induced cell cycle arrest. HCT116 p53-/- cells had less inflammatory responses. In a mouse model of Salmonella infection, intestinal epithelial p53 acetylation was increased by AvrA expression. Our studies provide novel mechanistic evidence that Salmonella modulates the p53 pathway during intestinal inflammation and infection.

  11. Micronutrients, N-acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression

    NARCIS (Netherlands)

    R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); G. Reid (Gregor)

    2010-01-01

    textabstractLow serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical t

  12. Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, A Review of Effectiveness in Reducing HIV Progression

    NARCIS (Netherlands)

    R.B.S. Hummelen (Ruben); J. Hemsworth (Jaimie); G.K. Reid (Gregor)

    2010-01-01

    textabstractLow serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical t

  13. Data for global lysine-acetylation analysis in rice (Oryza sativa

    Directory of Open Access Journals (Sweden)

    Yehui Xiong

    2016-06-01

    Full Text Available Rice is one of the most important crops for human consumption and is a staple food for over half of the world׳s population (Yu et al., 2002 [1]. A systematic identification of the lysine acetylome was performed by our research (Xiong et al., 2016 [2]. Rice plant samples were collected from 5 weeks old seedlings (Oryza sativa, Nipponbare. After the trypsin digestion and immunoaffinity precipitation, LC–MS/MS approach was used to identify acetylated peptides. After the collected MS/MS data procession and GO annotation, the InterProScan was used to annotate protein domain. Subcellular localization of the identified acetylated proteins was predicted by WoLF PSORT. The KEGG pathway database was used to annotate identified acetylated protein interactions, reactions, and relations. The data, supplied in this article, are related to “A comprehensive catalog of the lysine-acetylation targets in rice (O. sativa based on proteomic analyses” by Xiong et al. (2016 [2].

  14. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

    International Nuclear Information System (INIS)

    Research highlights: → Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. → PXR undergoes dynamic deacetylation upon ligand-mediated activation. → SIRT1 partially mediates PXR deacetylation. → PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.

  15. Hydrolytic stability of water-soluble spruce O-acetyl galactoglucomannans

    NARCIS (Netherlands)

    Xu, C.; Pranovich, A.; Hemmimg, J.; Holmbom, B.; Albrecht, S.A.; Schols, H.A.; Willfor, S.

    2009-01-01

    Water-soluble native O-acetyl galactoglucomannan (GGM) from spruce is a polysaccharide that can be produced in an industrial scale. To develop GGM applications, information is needed on its stability, particularly under acidic conditions. Therefore, acid hydrolysis of spruce GGM was investigated at

  16. On the Correlation between EPR and Positron Annihilation Measurements on gamma-Irradiated Acetyl Methionine

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Lund-Thomsen, E.; Mogensen, O. E.

    1972-01-01

    The dose dependence of the relative EPR signal intensity and positron lifetime spectrum was measured for γ‐irradiated acetyl methionine in the dose range from 0 to 30 Mrad. Angular correlation measurements were performed for the doses 0 and 30 Mrad. The result of the irradiation was the creation...

  17. Baker’s Yeast Mediated Reduction of 2-Acetyl-3-methyl Sulfolane

    Directory of Open Access Journals (Sweden)

    Rebecca E. Deasy

    2014-06-01

    Full Text Available The baker’s yeast mediated reduction of 2-acetyl-3-methyl sulfolane 1 to provide the corresponding alcohol 2 is described. Excellent efficiency and enantioselectivity (>98% ee has been achieved under these mild environmentally benign reaction conditions. In direct contrast, the chemical reduction of 1 proceeds with poor yield (≤25% and diastereocontrol.

  18. Acetylation regulates WRN catalytic activities and affects base excision DNA repair

    DEFF Research Database (Denmark)

    Muftuoglu, Meltem; Kusumoto, Rika; Speina, Elzbieta;

    2008-01-01

    The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone...

  19. N-Heterocyclic Carbene-Catalyzed Alcohol Acetylation: An Organic Experiment Using Organocatalysis

    Science.gov (United States)

    Morgan, John P.; Shrimp, Jonathan H.

    2014-01-01

    Undergraduate students in the teaching laboratory have successfully used N-heterocyclic carbenes (NHCs) as organocatalysts for the acetylation of primary alcohols, despite the high water sensitivity of uncomplexed ("free") NHCs. The free NHC readily reacted with chloroform, resulting in an air- and moisture-stable adduct that liberates…

  20. Acetylation stimulates the epithelial sodium channel by reducing its ubiquitination and degradation.

    Science.gov (United States)

    Butler, Phillip L; Staruschenko, Alexander; Snyder, Peter M

    2015-05-15

    The epithelial Na(+) channel (ENaC) functions as a pathway for Na(+) absorption in the kidney and lung, where it is crucial for Na(+) homeostasis and blood pressure regulation. ENaC is regulated in part through signaling pathways that control the ubiquitination state of ENaC lysines. A defect in ubiquitination causes Liddle syndrome, an inherited form of hypertension. Here we determined that α-, β-, and γENaC are also substrates for lysine acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, enhanced ENaC acetylation and increased ENaC abundance in the total cell lysate and at the cell surface. Moreover, TSA increased ENaC current in Fischer rat thyroid and kidney collecting duct epithelia. We found that HDAC7 is expressed in the kidney collecting duct, supporting a potential role for this histone deacetylase in ENaC regulation. HDAC7 overexpression reduced ENaC abundance and ENaC current, whereas ENaC abundance and current were increased by silencing of HDAC7. ENaC and HDAC7 form a complex, as detected by coimmunoprecipitation. We observed a reciprocal relationship between acetylation and ubiquitination; TSA reduced ENaC ubiquitination, whereas HDAC7 increased ubiquitination. By reducing ENaC ubiquitination, TSA decreased the rate of ENaC degradation. Thus, acetylation increases epithelial Na(+) absorption by antagonizing ENaC ubiquitination. This stabilizes ENaC, and hence, increases its abundance at the cell surface. PMID:25787079

  1. Green starch conversions : Studies on starch acetylation in densified CO2

    NARCIS (Netherlands)

    Muljana, Henky; Picchioni, Francesco; Heeres, Hero J.; Janssen, Leon P. B. M.

    2010-01-01

    The acetylation of potato starch with acetic anhydride (AAH) and sodium acetate (NaOAc) as catalyst in densified CO2 was explored in a batch reactor setup. The effects of process variables such as pressure (6-9.8 MPa), temperature (40-90 degrees C), AAH to starch ratio (2-5 mol/mol AGU), NaOAc to st

  2. Properties of retrograded and acetylated starch produced via starch extrusion or starch hydrolysis with pullulanase.

    Science.gov (United States)

    Kapelko, M; Zięba, T; Gryszkin, A; Styczyńska, M; Wilczak, A

    2013-09-12

    The aim of the present study was to determine the impact of serial modifications of starch, including firstly starch extrusion or hydrolysis with pullulanase, followed by retrogradation (through freezing and defrosting of pastes) and acetylation (under industrial conditions), on its susceptibility to amylolysis. The method of production had a significant effect on properties of the resultant preparations, whilst the direction and extent of changes depended on the type of modification applied. In the produced starch esters, the degree of substitution, expressed by the per cent of acetylation, ranged from 3.1 to 4.4 g/100 g. The acetylation had a significant impact on contents of elements determined with the atomic emission spectrometry, as it contributed to an increased Na content and decreased contents of Ca and K. The DSC thermal characteristics enabled concluding that the modifications caused an increase in temperatures and a decrease in heat of transition (or its lack). The acetylation of retrograded starch preparations increased their solubility in water and water absorbability. The modifications were found to exert various effects on the rheological properties of pastes determined based on the Brabender's pasting characteristics and flow curves determined with the use of an oscillatory-rotating viscosimeter. All starch acetates produced were characterized by ca. 40% resistance to amylolysis.

  3. Acetylated analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, S P; Longley, R E; Isbrucker, R A

    2001-02-01

    A series of eight discodermolide acetates have been prepared using natural (+)-discodermolide and evaluated for in vitro cytotoxicity against the cultured murine P-388 leukemia cells. The acetylated analogues showed a significant variation of cytotoxicity and suggested the importance of C-11 and C-17 hydroxyl groups for potency. The preparation and structure elucidation of the new analogues are described.

  4. Kinetics of Acid Hydrolysis of Water-Soluble Spruce O-Acetyl Galactoglucomannans

    NARCIS (Netherlands)

    Xu, C.; Pranovich, A.; Vahasalo, L.; Hemming, J.; Holmbom, B.; Schols, H.A.; Willfor, S.

    2008-01-01

    Water-soluble O-acetyl galactoglucomannan (GGM) is a softwood-derived polysaccharide, which can be extracted on an industrial scale from wood or mechanical pulping waters and now is available in kilogram scale for research and development of value-added products. To develop applications of GGM, info

  5. Calreticulin transacetylase mediates the acetylation of nitric oxide synthase by polyphenolic acetate

    NARCIS (Netherlands)

    Bansal, S.; Gaspari, M.; Raj, H.G.; Kumar, A.; Cuda, G.; Verheij, E.; Tyagi, Y.K.; Ponnan, P.; Rastogi, R.C.; Parmar, V.S.

    2008-01-01

    Our earlier investigations identified acetoxy drug: protein transacetylase (TAase), a unique enzyme in the endoplasmic reticulum (ER) catalyzing the transfer of acetyl groups from polyphenolic acetates (PA) to certain functional proteins. Recently we have established the identity of TAase with ER pr

  6. Effect of acetyl-SDKP, an inhibitor of hematopoiesis, in myelosuppressed animals

    International Nuclear Information System (INIS)

    The hemoregulatory tetrapeptide Acetyl-SDKP could be used as a myeloprotector in cancer chemotherapy as well as in radiobiology. It improves the survival rate in lethally irradiated rats and stimulates the leucocyte recovery in 1-β-D-arabino-furanosylcytosine treated cynomolgus monkeys

  7. Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation

    DEFF Research Database (Denmark)

    Weinert, Brian T; Schölz, Christian; Wagner, Sebastian A;

    2013-01-01

    . cerevisiae), human (HeLa) cells, and mouse liver tissue, demonstrating widespread succinylation in diverse organisms. A majority of succinylation sites in bacteria, yeast, and mouse liver were acetylated at the same position. Quantitative analysis of succinylation in yeast showed that succinylation was globally...

  8. Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays

    Science.gov (United States)

    Mishra, Laxmi N.; Pepenella, Sharon; Rogge, Ryan; Hansen, Jeffrey C.; Hayes, Jeffrey J.

    2016-01-01

    The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation. PMID:27708426

  9. A Bacillus licheniformis pectin acetylesterase is specific for homogalacturonans acetylated at O-3

    NARCIS (Netherlands)

    Remoroza, C.A.; Wagenknecht, M.; Buchholt, H.C.; Moerschbacher, B.M.; Schols, H.A.; Gruppen, H.

    2014-01-01

    A recombinant acetylesterase from Bacillus licheniformis DSM13, belonging to carbohydrate esterase family 12, was purified and biochemically characterized. The purified enzyme, termed BliPAE, was capable of deacetylating acetylated pectins, e.g. sugar beet pectin (SBP). Contrary to its provisional a

  10. The in situ distribution of glycoprotein-bound 4-O-Acetylated sialic acids in vertebrates.

    Science.gov (United States)

    Aamelfot, Maria; Dale, Ole Bendik; Weli, Simon Chioma; Koppang, Erling Olaf; Falk, Knut

    2014-05-01

    Sialic acids are located at the terminal branches of the cell glycocalyx and secreted glycan molecules. O-Acetylation is an important modification of the sialic acids, however very few studies have demonstrated the in situ distribution of the O-Acetylated sialic acids. Here the distribution of glycoprotein bound 4-O-Acetylated sialic acids (4-O-Ac sias) in vertebrates was determined using a novel virus histochemistry assay. The 4-O-Ac sias were found in the circulatory system, i.e. on the surface of endothelial cells and RBCs, of several vertebrate species, though most frequently in the cartilaginous fish (class Chondrichthyes) and the bony fish (class Osteichthyes). The O-Acetylated sialic acid was detected in 64 % of the examined fish species. Even though the sialic acid was found less commonly in higher vertebrates, it was found at the same location in the positive species. The general significance of this endothelial labelling pattern distribution is discussed. The seemingly conserved local position through the evolution of the vertebrates, suggests an evolutionary advantage of this sialic acid modification. PMID:24833039

  11. Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics

    Science.gov (United States)

    Protein lysine acetylation (LysAc) in bacteria has recently been demonstrated to be widespread in E. coli and Salmonella and to broadly regulate bacterial physiology and metabolism. However, LysAc in plant pathogenic bacteria is largely unknown. Here we report the lysine acetylome of Erwinia amylovo...

  12. Siylated and acetylated β-cyclodextrins for gas chromatographic stationary phases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Two new chiral stationary phases, 2,3-di-O-acetyl-6-O-trimethylsilyl-β-cyclodextrin (DATBCD)and 2, 6-di-O-trimethylsilyl-3-O-acetyl-β-cyclodextrin (DTABCD), were synthesized, their structures were identified by memos of infrared and NMB spectra. Capillary columns were coated with the two stationary- phases by dynamic method. The chromatographic properties, and enantiomers separation, such as ketone, esters, alcohols and olefines, were investigated on the silylated and acetylated β-cyclodextrin stationary phases. The expehmental results show that the silylated and acetylated β-cyclodextrins are suitable to be used as capillary gas chromatographic stationary phases, the relative polarity of DATBCD and DTABCD stationary phases is respectively 4143 and 3928, the colmnn efficiencies are respectively 3084 and 4198, and DATBCD is of stronger enantioselectivity- than DTABCD, capacity factor of the first eluted enantiomer ( k1 ) and separation factor(α)of α-phenylethanol on DATBCD stationary phase are respectively 8.23 and 1.019.

  13. Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression

    Directory of Open Access Journals (Sweden)

    Shang-Jui Wang

    2016-10-01

    Full Text Available Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53. Whereas the loss of K98 acetylation (p53K98R alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R] completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p533KR, p534KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p534KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.

  14. Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Ying-Xuan Chen; Jing-Yuan Fang; Hong-Yin Zhu; Rong Lu; Zhong-Hua Cheng; De-Kai Qiu

    2004-01-01

    AIM: To investigate the effect of histone acetylation on regulation of p21WAF1 gene expression in human colon cancer cell lines.METHODS: Two cell lines, Colo-320 and SW1116 were treated with either trichostatin or sodium butyrate. Expressions of p21WAF1 mRNA and protein were detected by real-time RT-PCR and Western blotting, respectively. Acetylation of two regions of p21WAF1 gene-associated histones and total cellular histones were examined by chromatin immunoprecipitation assay and Western blotting. RESULTS: Trichostatin or sodium butyrate re-activated p21WAF1 transcription resulted in up-regulated p21WF1 protein level in colon cancer cell lines. Those effects were accompanied by an accumulation of acetylated histones in total cellular chromatin and p21WAF1 gene-associated region of chromatin.CONCLUSION: Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116.

  15. Acetyl Coenzyme A Acetyltransferase of Rhizobium sp. (Cicer) Strain CC 1192.

    Science.gov (United States)

    Kim, S A; Copeland, L

    1997-09-01

    To investigate why Rhizobium sp. (Cicer) strain CC 1192 cells accumulate poly-R-3-hydroxybutyrate in the free-living state but not as bacteroids in nodules on chickpea (Cicer arietinum L.) plants, we have examined the kinetic properties of acetyl coenzyme A (acetyl-CoA) acetyltransferase (also known as acetoacetyl-CoA thiolase and 3-ketothiolase [EC 2.3.1.9]) from both types of cells. The enzyme had a native molecular mass of 180 (plusmn) 4 kDa, and the subunit molecular mass was 44 (plusmn) 1 kDa. The seven amino acids from the N terminus were Lys-Ala-Ser-Ile-Val-Ile-Ala. Thiolysis and condensation activity of the enzyme from free-living CC 1192 cells were optimal at pHs 7.8 and 8.1, respectively. The relationship between substrate concentrations and initial velocity for the thiolysis reaction were hyperbolic and gave K(infm) values for acetoacetyl-CoA and CoA of 42 and 56 (mu)M, respectively. The maximum velocity in the condensation direction was approximately 10% of that of the thiolysis reaction. With highly purified preparations of the enzyme, a value of approximately 1 mM was determined for the apparent K(infm) for acetyl-CoA. However, with partially purified enzyme preparations or when N-ethylmaleimide was included in reaction mixtures the apparent K(infm) for acetyl-CoA was close to 0.3 mM. In the condensation direction, CoA was a potent linear competitive inhibitor with an inhibition constant of 11 (mu)M. The much higher affinity of the enzyme for the product CoA than the substrate acetyl-CoA could have significance in view of metabolic differences between bacteroid and free-living cells of CC 1192. We propose that in free-living CC 1192 cells, the acetyl-CoA/CoA ratio reaches a value that allows condensation activity of acetyl-CoA acetyltransferase, but that in CC 1192 bacteroids, the ratio is poised so that the formation of acetoacetyl-CoA is not favored.

  16. 17β-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice

    OpenAIRE

    Fortress, Ashley M.; Kim, Jaekyoon; Rachel L Poole; Gould, Thomas J.; Frick, Karyn M.

    2014-01-01

    Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17β-estradiol (E2) to enhance object recognition memory consolidation requires histone H3 acetylation in the dorsal hippocampus. However, the extent to which histone ace...

  17. p53 acetylation enhances Taxol-induced apoptosis in human cancer cells.

    Science.gov (United States)

    Kim, Jae Hyeong; Yoon, Eun-Kyung; Chung, Hye-Jin; Park, Seong-Yeol; Hong, Kyeong-Man; Lee, Chang-Hun; Lee, Yeon-Su; Choi, Kyungho; Yang, Young; Kim, Kyungtae; Kim, In-Hoo

    2013-01-01

    Microtubule inhibitors (MTIs) such as Taxol have been used for treating various malignant tumors. Although MTIs have been known to induce cell death through mitotic arrest, other mechanisms can operate in MTI-induced cell death. Especially, the role of p53 in this process has been controversial for a long time. Here we investigated the function of p53 in Taxol-induced apoptosis using p53 wild type and p53 null cancer cell lines. p53 was upregulated upon Taxol treatment in p53 wild type cells and deletion of p53 diminished Taxol-induced apoptosis. p53 target proteins including MDM2, p21, BAX, and β-isoform of PUMA were also upregulated by Taxol in p53 wild type cells. Conversely, when the wild type p53 was re-introduced into two different p53 null cancer cell lines, Taxol-induced apoptosis was enhanced. Among post-translational modifications that affect p53 stability and function, p53 acetylation, rather than phosphorylation, increased significantly in Taxol-treated cells. When acetylation was enhanced by anti-Sirt1 siRNA or an HDAC inhibitor, Taxol-induced apoptosis was enhanced, which was not observed in p53 null cells. When an acetylation-defective mutant of p53 was re-introduced to p53 null cells, apoptosis was partially reduced compared to the re-introduction of the wild type p53. Thus, p53 plays a pro-apoptotic role in Taxol-induced apoptosis and acetylation of p53 contributes to this pro-apoptotic function in response to Taxol in several human cancer cell lines, suggesting that enhancing acetylation of p53 could have potential implication for increasing the sensitivity of cancer cells to Taxol.

  18. Preparation and characterization of acetylated starch nanoparticles as drug carrier: Ciprofloxacin as a model.

    Science.gov (United States)

    Mahmoudi Najafi, Seyed Heydar; Baghaie, Maryam; Ashori, Alireza

    2016-06-01

    The objective of this study was to characterize in-vitro the potential of acetylated corn starch (ACS) particles as a matrix for the delivery of ciprofloxacin (CFx). ACS was successfully synthesized and optimized by the reaction of native corn starch using acetic anhydride and acetic acid with low and high degrees of substitution (DS). The nanoprecipitation method was applied for the formation of the ACS-based nanoparticles, by the dropwise addition of water to acetone solution of ACS under stirring. The effects of acetylation and nanoprecipitation on the morphology and granular structure of ACS samples were examined by the FT-IR, XRD, DSL and SEM techniques. The efficiency of CFx loading was also evaluated via encapsulation efficiency (EE) in ACS nanoparticles. The average degree of acetyl substitution per glucose residue of corn starch was 0.33, 2.00, and 2.66. The nanoparticles size of the ACS and ACS-loaded with CFx were measured and analyzed relative to the solvent:non-solvent ratio. Based on the results, ACS nanoparticles with DS of 2.00 and water:acetone of 3:1 had 312nm diameter. Increasing DS in starch acetate led to increase in the EE from 67.7 to 89.1% and with increasing ratio of water/acetone from 1:1 to 3:1, the EE raised from 48.5 to 89.1%. X-ray diffraction indicated that A-type pattern of native starch was completely transformed into the V-type pattern of acetylated starch. The scanning electron microscopy showed that the different sizes of pores formed on the acetylated starch granules were utterly converted into the uniform-sized spherical nanoparticles after the nanoprecipitation. PMID:26893054

  19. Purification and characterization of the acetyl-CoA synthetase from Mycobacterium tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Ru Li; Jing Gu; Peng Chen; Zhiping Zhang; Jiaoyu Deng; XianEn Zhang

    2011-01-01

    Acetyl-CoA (AcCoA) synthetase (Acs) catalyzes the conversion of acetate into AcCoA,which is involved in many catabolic and anabolic pathways.Although this enzyme has been studied for many years in many organisms,the properties of Mycobacterium tuberculosis Acs and the regulation of its activity remain unknown.Here,the putative acs gene of M.tuberculosis H37Rv (Mt-Acs) was expressed as a fusion protein with 6×His-tag on the C-terminus in Escherichia coli.The recombinant Mt-Acs protein was successfully purified and then its enzymatic characteristics were analyzed.The optimal pH and temperature,and the kinetic parameters of Mt-Acs were determined.To investigate whether Mt-Acs is regulated by lysine acetylation as reported for Salmonella enterica Acs,its mutant K617R was also generated.Determination of the enzymatic activity suggests that Lys-617 is critical for its function.We further demonstrated that Mt-Acs underwent auto-acetylation with acetate but not with AcCoA as the acetyl donor,which resulted in the decrease of its activity.CoA,the substrate for AcCoA formation,inhibited the auto-acetylation.Furthermore,the silent information regulator (Sir2) of M.tuberculosis (Mt-Sir2) could catalyze Mt-Acs deacetylation,which resulted in activation of Acs.These results may provide more insights into the physiological roles of Mt-Acs in M.tuberculosis central metabolism.

  20. 17ß-Estradiol Regulates Histone Alterations Associated with Memory Consolidation and Increases "Bdnf" Promoter Acetylation in Middle-Aged Female Mice

    Science.gov (United States)

    Fortress, Ashley M.; Kim, Jaekyoon; Poole, Rachel L.; Gould, Thomas J.; Frick, Karyn M.

    2014-01-01

    Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age-related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17ß-estradiol…

  1. Determination of the degree of acetylation and the distribution of acetyl groups in chitosan by HPLC analysis of nitrous acid degraded and PMP labeled products.

    Science.gov (United States)

    Han, Zhangrun; Zeng, Yangyang; Lu, Hong; Zhang, Lijuan

    2015-09-01

    Chitin is one of the most abundant polysaccharides on earth. It consists of repeating β-1,4 linked N-acetylated glucosamine (A) units. Chitosan is an N-deacetylated product of chitin. Chitosan and its derivatives have broad medical applications as drugs, nutraceuticals, or drug delivery agents. However, a reliable analytical method for quality control of medically used chitosans is still lacking. In current study, nitrous acid was used to cleave all glucosamine residues in chitosan into 2,5-anhydromannose (M) or M at the reducing end of di-, tri-, and oligosaccharides. PMP, i.e. 1-phenyl-3-methyl-5-pyrazolone, was used to label all the Ms. Online UV detection allowed quantification of all M-containing UV peaks whereas online MS analysis directly identified 11 different kinds of mono-, di-, tri-, and oligosaccharides that correlated each oligosaccharide with specific UV peak after HPLC separation. The DA (degree of acetylation) for chitosans was calculated based on the A/(A+M) value derived from the UV data. This newly developed method had several advantages for quality control of chitosan: 1. the experimental procedures were extensively optimized; 2. the reliability of the method was confirmed by online LC-MS analysis; 3. the DA value was obtainable based on the UV data after HPLC analysis, which was comparableto that of (1)H NMR and conductometric titration analyses; 4. finally and most importantly, this method could be used to obtain the DA as well as chemical acetylation/deacetylation mechanisms for chitosan by any laboratory equipped with a HPLC and an online UV detector.

  2. Binary and tertiary combination of alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol on HepG2 cells: Toxic effects and evaluation of degradation products.

    Science.gov (United States)

    Juan-García, Ana; Juan, Cristina; Manyes, Lara; Ruiz, María-José

    2016-08-01

    Fungi producers of mycotoxins are able to synthesize more than one toxin. Alternariol (AOH) is one of the mycotoxins produced by several Alternaria species, the most common one being Alternaria alternata. The toxins 3-Acetyl-deoxynivalenol (3-ADON) and 15-Acetyl-deoxynivalenol (15-ADON) are acetylated forms of deoxynivalenol (DON) produced by Fusarium graminearum. In the present work it is determined and evaluated the toxic effects of binary and tertiary combination treatment of HepG2 cells with AOH, 3-ADON and 15-ADON, by using the MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), to subsequently apply the isobologram method and elucidate if the mixtures of these mycotoxins produced synergism, antagonism or additive effect; and lastly, to analyze mycotoxins conversion into metabolites produced and released by HepG2 cells after applying the treatment conditions by liquid chromatography tandem mass spectrometry (LC-MS/MS) equipment and extracted from culture media. HepG2 cells were treated at different concentrations over 24, 48 and 72h. IC50 values detected at all times assayed, ranged from 0.8 to >25μM in binary combinations; while in tertiary it ranged from 7.5 to 12μM. Synergistic, antagonism or additive effect detected in the mixtures of these mycotoxins was different depending on low or high concentration. Among all four mycotoxins combinations assayed, 15-ADON+3-ADON presented the highest toxic potential. At all assayed times, recoveries values oscillated depending on the time and combination studied. PMID:27131905

  3. Upregulation of mGlu2 receptors via NF-κB p65 acetylation is involved in the Proneurogenic and antidepressant effects of acetyl-L-carnitine.

    Science.gov (United States)

    Cuccurazzu, Bruna; Bortolotto, Valeria; Valente, Maria Maddalena; Ubezio, Federica; Koverech, Aleardo; Canonico, Pier Luigi; Grilli, Mariagrazia

    2013-10-01

    Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-κB p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-κB pathway, and in particular by p65 acetylation, and subsequent NF-κB-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressants. PMID:23670591

  4. Ecdysone induced gene expression is associated with acetylation of histone H3 lysine 23 in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    László Bodai

    Full Text Available Posttranslational modification of histones regulates transcription but the exact role that acetylation of specific lysine residues plays in biological processes in vivo is still not clearly understood. To assess the contribution of different histone modifications to transcriptional activation in vivo, we determined the acetylation patterns on the ecdysone induced Eip74EF and Eip75B genes in Drosophila melanogaster larvae by chromatin immunoprecipitation. We found that acetylation of histone H3 lysine 23 is localized to promoters and correlates with endogenous ecdysone induced gene activation. In contrast, acetylation of lysines 8, 12 and 16 of histone H4 and lysine 9 of histone H3 showed minor differences in their distribution on the regulatory and transcribed regions tested, and had limited or no correlation with ecdysone induced transcriptional activity. We found that dCBP, which is encoded by the nejire gene, acetylates H3 lysine 23 in vivo, and silencing of nejire leads to reduced expression of the Eip74EF and Eip75B genes. Our results suggest that acetylation of specific lysine residues of histones contribute specifically to the dynamic regulation of transcription. Furthermore, along with previous studies identify CBP dependent H3 lysine 23 acetylation as an evolutionarily conserved chromatin modification involved in steroid induced gene activation.

  5. Probing the interaction of spermine and 1-naphthyl acetyl spermine with DNA polynucleotides: a comparative biophysical and thermodynamic investigation.

    Science.gov (United States)

    Kabir, Ayesha; Kumar, Gopinatha Suresh

    2014-05-01

    The interaction of spermine and its analogue, 1-naphthyl acetyl spermine with four double stranded DNA polynucleotides has been studied to understand the structural and thermodynamic basis of the binding. The efficacy and specificity of DNA binding of this analogue has not yet been revealed. The energetics of the interaction was studied by isothermal titration calorimetry and differential scanning calorimetry. Circular dichroism spectroscopy, UV-thermal melting and ethidium bromide displacement assay have been employed to characterize the association. Circular dichroism studies showed that 1-naphthyl acetyl spermine caused a stronger structural perturbation in the polynucleotides. Among the adenine-thymine polynucleotides the alternating polynucleotide was more preferred by naphthyl acetyl spermine compared to the preference of spermine for the homo sequence. The higher melting stabilization revealed by the optical melting and differential scanning calorimetry results suggested that the binding of 1-naphthyl acetyl spermine increased the melting temperature and the total standard molar enthalpy of the transition of adenine-thymine polynucleotides. Microcalorimetry results revealed that unlike spermine the binding of 1-naphthyl acetyl spermine was endothermic. The interaction was characterized by total enthalpy-entropy compensation and high standard molar heat capacity values. There are differences in the mode of association of 1-naphthyl acetyl spermine and spermine. 1-naphthyl acetyl spermine binds with an enhanced affinity with the adenine-thymine hetero polynucleotide. Thus, the result suggests the importance of polyamine analogues and their ability to interfere with normal polyamine interactions.

  6. Pyruvate dehydrogenase and 3-fluoropyruvate: chemical competence of 2-acetylthiamin pyrophosphate as an acetyl group donor to dihydrolipoamide

    International Nuclear Information System (INIS)

    The pyruvate dehydrogenase component (E1) of the pyruvate dehydrogenase complex catalyzes the decomposition of 3-fluoropyruvate to CO2, fluoride anion, and acetate. Acetylthiamin pyrophosphate (acetyl-TPP) is an intermediate in this reaction. Incubation of the pyruvate dehydrogenase complex with 3-fluoro[1,2-14]pyruvate, TPP, coenzyme A (CoASH), and either NADH or pyruvate as reducing systems leads to the formation of [14]acetyl-CoA. In this reaction the acetyl group of acetyl-TPP is partitioned by transfer to both CoASH (87 +/- 2%) and water (13 +/- 2%). When the E1 component is incubated with 3-fluoro[1,2-14]pyruvate, TPP, and dihydrolipoamide, [14]acetyldihydrolipoamide is produced. The formation of [14C]acetyldihydrolipoamide was examined as a function of dihydrolipoamide concentration (0.25-16 mM). A plot of the extent of acetyl group partitioning to dihydrolipoamide as a function of 1/[dihydrolipoamide] showed 95 +/- 2% acetyl group transfer to dihydrolipoamide when dihydrolipoamide concentration was extrapolated to infinity. It is concluded that acetyl-TPP is chemically competent as an intermediate for the pyruvate dehydrogenase complex catalyzed oxidative decarboxylation of pyruvate

  7. N-Acetyl cysteine restores viability and function of rat odontoblast-like cells impaired by polymethylmethacrylate dental resin extract.

    Science.gov (United States)

    Yamada, Masahiro; Kojima, Norinaga; Att, Wael; Hori, Norio; Suzuki, Takeo; Ogawa, Takahiro

    2009-01-01

    There is concern that dental-resin materials directly loaded on a prepared tooth adversely affect dental pulp tissue by releasing the resin chemicals through dentinal tubes. This study determined whether self-curing polymethyl methacrylate (PMMA)-based dental resin extract adversely affected the viability and function of odontoblast-like cells and whether the cytotoxicity of this resin, if any, could be eliminated by N-acetyl cysteine, an antioxidant amino acid derivative. Odontoblast-like cells isolated from rat maxillary incisor dental pulp tissue were exposed to a PMMA resin extract with or without N-acetyl cysteine for 1 h and then cultured in osteoblastic media. The percentage of viable cells 24 h after seeding was 20% in cells exposed to the resin extract without N-acetyl cysteine, whereas 45% of cells were viable after exposure to the N-acetyl cysteine-supplemented extract. The cells that had been exposed to the extract showed a strong tendency for apoptosis associated with the increased reactive oxygen species production and decreased intracellular glutathione level, which was improved by the addition of N-acetyl cysteine. N-Acetyl cysteine supplementation almost completely restored the significantly reduced alkaline phosphatase activity and matrix mineralization by the resin extract. These results conclusively demonstrated that exposure of odontoblast-like cells to the resin extract impaired the cell viability and function and, more intriguingly, N-acetyl cysteine supplementation to the extract significantly prevented these toxic effects.

  8. Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration.

    Science.gov (United States)

    Siudeja, Katarzyna; Srinivasan, Balaji; Xu, Lanjun; Rana, Anil; de Jong, Jannie; Nollen, Ellen A A; Jackowski, Suzanne; Sanford, Lynn; Hayflick, Susan; Sibon, Ody C M

    2011-12-01

    Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development. PMID:21998097

  9. Luminal localization of α-tubulin K40 acetylation by cryo-EM analysis of fab-labeled microtubules.

    Directory of Open Access Journals (Sweden)

    Virupakshi Soppina

    Full Text Available The αβ-tubulin subunits of microtubules can undergo a variety of evolutionarily-conserved post-translational modifications (PTMs that provide functional specialization to subsets of cellular microtubules. Acetylation of α-tubulin residue Lysine-40 (K40 has been correlated with increased microtubule stability, intracellular transport, and ciliary assembly, yet a mechanistic understanding of how acetylation influences these events is lacking. Using the anti-acetylated tubulin antibody 6-11B-1 and electron cryo-microscopy, we demonstrate that the K40 acetylation site is located inside the microtubule lumen and thus cannot directly influence events on the microtubule surface, including kinesin-1 binding. Surprisingly, the monoclonal 6-11B-1 antibody recognizes both acetylated and deacetylated microtubules. These results suggest that acetylation induces structural changes in the K40-containing loop that could have important functional consequences on microtubule stability, bending, and subunit interactions. This work has important implications for acetylation and deacetylation reaction mechanisms as well as for interpreting experiments based on 6-11B-1 labeling.

  10. Oxygen-dependent acetylation and dimerization of the corepressor CtBP2 in neural stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Karaca, Esra; Lewicki, Jakub; Hermanson, Ola, E-mail: Ola.Hermanson@ki.se

    2015-03-01

    The transcriptional corepressor CtBP2 is essential for proper development of the nervous system. The factor exerts its repression by interacting in complexes with chromatin-modifying factors such as histone deacetylases (HDAC) 1/2 and the histone demethylase LSD1/KDM1. Notably, the histone acetyl transferase p300 acetylates CtBP2 and this is an important regulatory event of the activity and subcellular localization of the protein. We recently demonstrated an essential role for CtBPs as sensors of microenvironmental oxygen levels influencing the differentiation potential of neural stem cells (NSCs), but it is not known whether oxygen levels influence the acetylation levels of CtBP factors. Here we show by using proximity ligation assay (PLA) that CtBP2 acetylation levels increased significantly in undifferentiated, proliferating NSCs under hypoxic conditions. CtBP2 interacted with the class III HDAC Sirt1 but this interaction was unaltered in hypoxic conditions, and treatment with the Sirt1 inhibitor Ex527 did not result in any significant change in total CtBP2 acetylation levels. Instead, we revealed a significant decrease in PLA signal representing CtBP2 dimerization in NSCs under hypoxic conditions, negatively correlating with the acetylation levels. Our results suggest that microenvironmental oxygen levels influence the dimerization and acetylation levels, and thereby the activity, of CtBP2 in proliferating NSCs.

  11. Spectroscopic and Biological Studies on Newly Synthesized Cobalt (II and Nickel (II Complexes with 2-Acetyl Coumarone Semicarbazone and 2-Acetyl Coumarone Thiosemicarbazone

    Directory of Open Access Journals (Sweden)

    Sanjay Goel

    2013-01-01

    Full Text Available Co(II and Ni(II complexes of general composition ML2X2 (M = Co(II, Ni(II; X = Cl−, NO3 − were synthesized by the condensation of metal salts with semicarbazone/thiosemicarbazone derived from 2-acetyl coumarone. The ligands and metal complexes were characterized by NMR, elemental analysis, molar conductance, magnetic susceptibility measurements, IR, and atomic absorption spectral studies. On the basis of electronic, molar conductance and infrared spectral studies, the complexes were found to have square planar geometry. The Schiff bases and their metal complexes were tested for their antibacterial and antioxidant activities.

  12. Stability and Analgesic Efficacy of Di-acetyl Morphine (Diamorphine) Compared with Morphine in Implanted Intrathecal Pumps In Vivo.

    Science.gov (United States)

    Raphael, Jon H; Palfrey, Stephen M; Rayen, Arasu; Southall, Jane L; Labib, Maurad H

    2004-07-01

    The objective of this study was to investigate di-acetyl morphine as an alternative opioid analgesic for use in implanted intrathecal drug delivery systems because of its greater solubility through evaluation of its stability in vivo and analgesic efficacy in the period between pump refills. Contents of intrathecal drug delivery system reservoirs (SynchroMed, Medtronic, Inc., Minneapolis, MN) that had been filled with di-acetyl morphine dissolved in saline (21), bupivacaine (9), or in both bupivacaine and clonidine (19) were sampled in vivo between 1 and 125 days after refill. The samples were assayed for di-acetyl morphine and its breakdown products by micellar electrokinetic capillary chromatography. Prospective daily numerical pain scores between pump refills, using 11-point Likert scales, on 24 patients with implanted SynchroMed pumps (12 delivering di-acetyl morphine in saline, 12 were delivering morphine in saline) were collected. Results showed that di-acetyl morphine immediately started to decay to mono-acetyl morphine in implanted Synchromed pumps with half-life of 50 days. Mono-acetyl morphine decayed to morphine with a maxima estimated at 125 days. There was no clinically significant change in average weekly pain scores for up to ten weeks in either group (range, 2.5 to 2.8 for diamorphine and 2.7 to 3.1 for morphine) (2-way repeated ANOVA, F(9,220) = 0.98, n.s.). We conclude that di-acetyl morphine and its breakdown products, 6 mono-acetyl morphine and morphine, provide similar analgesia to morphine alone when administered by intrathecal pump for a period of at least ten weeks and may be a useful alternative when a more soluble agent is favored. PMID:22151270

  13. N-Acetyl-L-Leucine Accelerates Vestibular Compensation after Unilateral Labyrinthectomy by Action in the Cerebellum and Thalamus

    OpenAIRE

    Lisa Günther; Roswitha Beck; Guoming Xiong; Heidrun Potschka; Klaus Jahn; Peter Bartenstein; Thomas Brandt; Mayank Dutia; Marianne Dieterich; Michael Strupp; Christian la Fougère; Andreas Zwergal

    2015-01-01

    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular beha...

  14. On the Mechanism of Condensation between 5-Amino-4, 6-dichloro-2-methylpyrimidine and 1-Acetyl-2-imidazolin-2-one

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The condensation reaction between 5-amino-4, 6-dichloro-2-methylpyrimidine and 1-acetyl-2-imidazolin-2-one using POCl3 as solvent gave 4, 6-dichloro-2-methyl-5-(l-acetyl-tetrahydro-imidazo-2-ylidene)-aminopyrimidine predominantly and 4, 6-dichloro-2-methyl-5-{1-[ l-(2-oxo-tetrahydro-imidazolyl)]-acetyene}-aminopyrimidine as by-product. No 4, 6-dichloro-2-methyl-5-(1-acetyl-2-imidazolin-2-yl)-aminopyrimidine was found. The result indicated an esterifi- cation-addition-elimination mechanism.``

  15. Functional Interplay between Acetylation and Methylation of the RelA Subunit of NF-κB▿

    OpenAIRE

    Yang, Xiao-Dong; Tajkhorshid, Emad; Chen, Lin-Feng

    2010-01-01

    Posttranslational modifications of the RelA subunit of NF-κB, including acetylation and methylation, play a key role in controlling the strength and duration of its nuclear activity. Whether these modifications are functionally linked is largely unknown. Here, we show that the acetylation of lysine 310 of RelA impairs the Set9-mediated methylation of lysines 314 and 315, which is important for the ubiquitination and degradation of chromatin-associated RelA. Abolishing the acetylation of lysin...

  16. Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65

    OpenAIRE

    Buerki, C; Rothgiesser, K M; Valovka, T; Owen, H R; Rehrauer, H; Fey, M.; Lane, W S; Hottiger, M O

    2008-01-01

    Nuclear factor kappaB (NF-kappaB) plays an important role in the transcriptional regulation of genes involved in immunity and cell survival. We show here in vitro and in vivo acetylation of RelA/p65 by p300 on lysine 314 and 315, two novel acetylation sites. Additionally, we confirmed the acetylation on lysine 310 shown previously. Genetic complementation of RelA/p65-/- cells with wild type and non-acetylatable mutants of RelA/p65 (K314R and K315R) revealed that neither shuttling, DNA binding...

  17. Synthesis and Molecular Structure of 1-Acetyl-1-(4-iodophenyl)-3-cyclohexylurea

    Institute of Scientific and Technical Information of China (English)

    QIAN Qiu-Feng; ZOU Jian-Ping; MU Xue-Jun; ZENG Run-Sheng

    2006-01-01

    The title compound 1-acetyl-1-(4-iodophenyl)-3-cyclohexylurea 1 (C15H19IN2O2, Mr = 386.22) has been synthesized and its crystal structure was determined by X-ray diffraction analysis. It crystallizes in orthorhombic, space group Pbca, a =15.4754(16), b = 11.4284(11), c = 17.829(2) (A),Z = 8, V = 3153.2(6)(A)3, Dc= 1.627 mg/m3, μ(MoKα) = 2.034 mm-1, F(000) = 1536, the final R = 0.0276 and wR = 0.0593 for 2805 observed reflections (I > 2σ(I)). X-ray analysis reveals that cyclohexyl ring adopts a chair conformation, with the cyclohexyl group located at the 3-position of urea, and the acetyl and 4-iodophenyl groups at the 1-position.

  18. Effect of acetylation, oxidation and annealing on physicochemical properties of bean starch.

    Science.gov (United States)

    Simsek, Senay; Ovando-Martínez, Maribel; Whitney, Kristin; Bello-Pérez, Luis A

    2012-10-15

    Black and Pinto bean starches were physically and chemically modified to investigate the effect of modification on digestibility and physicochemical properties of bean starch. The impact of acetylation, oxidation (ozonation) and annealing on the chemical composition, syneresis, swelling volume, pasting, thermal properties and digestibility of starches was evaluated. The physicochemical and estimated glycemic index (eGI) of the Black and Pinto bean starches treated with ozone were not significantly (P>0.05) different than that of their respective control starches. Annealed starches had improved thermal and pasting properties compared to native starches. Acetylated starches presented reduced syneresis, good pasting properties and lower eGI. Also, all modified starches had increased levels of resistant starch (RS). Therefore, the digestibility and physicochemical properties of bean starch were affected by the type of modification but there were no significant (P>0.05) differences between the Black and Pinto bean starches.

  19. CHITOSAN SOLUTIONS WITH DIFFERENT DEGREES OF ACETYLATION AS COATING ON CUT APPLE

    Directory of Open Access Journals (Sweden)

    Douglas de BRITTO

    2012-01-01

    Full Text Available In this study we analyzed the protective properties of different types of chitosan on minimally processed apples, concerning water loss, surface color changes and antifungal activity. Seven different chitosanbased formulations with variable molecular weight and degrees of acetylation were prepared and used to coat sliced apples which were stored in a greenhouse at 28o C and RH 80%. The coatings, with concentration of 2.0g/L, independent of chitosan type, had no significant effect in protecting the samples against loss of mass by water vapor permeation. Along the storage time, all samples resulted in similar dehydration. Gradual browning was observed in cut fruit, whereas chitosan did not maintain natural color of the cut surfaces. Concerning antifungal activity, chitosans with low molecular weight and low degree of acetylation was the best formulation, reducing in around 50% the fungal incidence after 10 days of storage.

  20. Cigarette Smoking, N-Acetyltransferase 2 Acetylation Status, and Bladder Cancer Risk

    DEFF Research Database (Denmark)

    Marcus, P.M.; Hayes, R.B.; Vineis, P.;

    2000-01-01

    Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder...... cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize...... results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used...

  1. Inhibition of acetyl-CoA carboxylase by cystamine may mediate the hypotriglyceridemic activity of pantethine.

    Science.gov (United States)

    McCarty, M F

    2001-03-01

    Pantethine is a versatile and well-tolerated hypolipidemic agent whose efficacy in this regard appears to be mediated by its catabolic product cystamine, a nucleophile which avidly attacks disulfide groups. An overview of pantethine research suggests that the hypotriglyceridemic activity of pantethine reflects cystamine-mediated inhibition of the hepatic acetyl-CoA carboxylase, which can be expected to activate hepatic fatty acid oxidation. Inhibition of HMG-CoA reductase as well as a more distal enzyme in the cholesterol synthetic pathway may account for pantethine's hypocholesterolemic effects. If pantethine does indeed effectively inhibit hepatic acetyl-CoA carboxylase, it may have adjuvant utility in the hepatothermic therapy of obesity. As a safe and effective compound of natural origin, pantethine merits broader use in the management of hyperlipidemias. PMID:11359352

  2. Stereoselective Luche reduction of deoxynivalenol and three of its acetylated derivatives at C8.

    Science.gov (United States)

    Fruhmann, Philipp; Hametner, Christian; Mikula, Hannes; Adam, Gerhard; Krska, Rudolf; Fröhlich, Johannes

    2014-01-01

    The trichothecene mycotoxin deoxynivalenol (DON) is a well known and common contaminant in food and feed. Acetylated derivatives and other biosynthetic precursors can occur together with the main toxin. A key biosynthetic step towards DON involves an oxidation of the 8-OH group of 7,8-dihydroxycalonectrin. Since analytical standards for the intermediates are not available and these intermediates are therefore rarely studied, we aimed for a synthetic method to invert this reaction, making a series of calonectrin-derived precursors accessible. We did this by developing an efficient protocol for stereoselective Luche reduction at C8. This method was used to access 3,7,8,15-tetrahydroxyscirpene, 3-deacetyl-7,8-dihydroxycalonectrin, 15-deacetyl-7,8-dihydroxycalonectrin and 7,8-dihydroxycalonectrin, which were characterized using several NMR techniques. Beside the development of a method which could basically be used for all type B trichothecenes, we opened a synthetic route towards different acetylated calonectrins. PMID:24434906

  3. Regulation and structure of the heteromeric acetyl-CoA carboxylase.

    Science.gov (United States)

    Salie, Matthew J; Thelen, Jay J

    2016-09-01

    The enzyme acetyl-CoA carboxylase (ACCase) catalyzes the committed step of the de novo fatty acid biosynthesis (FAS) pathway by converting acetyl-CoA to malonyl-CoA. Two forms of ACCase exist in nature, a homomeric and heteromic form. The heteromeric form of this enzyme requires four different subunits for activity: biotin carboxylase; biotin carboxyl carrier protein; and α- and β-carboxyltransferases. Heteromeric ACCases (htACCase) can be found in prokaryotes and the plastids of most plants. The plant htACCase is regulated by diverse mechanisms reflected by the biochemical and genetic complexity of this multienzyme complex and the plastid stroma where it resides. In this review we summarize the regulation of the plant htACCase and also describe the structural characteristics of this complex from both prokaryotes and plants. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27091637

  4. BRPF3-HBO1 regulates replication origin activation and histone H3K14 acetylation

    DEFF Research Database (Denmark)

    Feng, Yunpeng; Vlassis, Arsenios; Roques, Céline;

    2016-01-01

    that specifically acetylates histone H3K14, and genomewide analysis shows high enrichment of BRPF3, HBO1 and H3K14ac at ORC1-binding sites and replication origins found in the vicinity of TSSs. Consistent with this, BRPF3 is necessary for H3K14ac at selected origins and efficient origin activation. CDC45...... recruitment, but not MCM2-7 loading, is impaired in BRPF3-depleted cells, identifying a BRPF3-dependent function of HBO1 in origin activation that is complementary to its role in licencing. We thus propose that BRPF3-HBO1 acetylation of histone H3K14 around TSS facilitates efficient activation of nearby...

  5. Kinetics of Mushroom Tyrosinase and Melanogenesis Inhibition by N-Acetyl-pentapeptides

    Directory of Open Access Journals (Sweden)

    Ching-Yi Lien

    2014-01-01

    Full Text Available We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR, and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the oxidation of L-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl-pentapeptides, only Ac-P4 exhibited lag time (80 s at a concentration of 0.5 mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC50 0.29 mg/mL were more effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL, 0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all 4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1 mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma cells and was more effective than kojic acid. The melanogenesis inhibition of Ac-P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma cells.

  6. Genome-wide histone acetylation is altered in a transgenic mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Karen N McFarland

    Full Text Available In Huntington's disease (HD; MIM ID #143100, a fatal neurodegenerative disorder, transcriptional dysregulation is a key pathogenic feature. Histone modifications are altered in multiple cellular and animal models of HD suggesting a potential mechanism for the observed changes in transcriptional levels. In particular, previous work has suggested an important link between decreased histone acetylation, particularly acetylated histone H3 (AcH3; H3K9K14ac, and downregulated gene expression. However, the question remains whether changes in histone modifications correlate with transcriptional abnormalities across the entire transcriptome. Using chromatin immunoprecipitation paired with microarray hybridization (ChIP-chip, we interrogated AcH3-gene interactions genome-wide in striata of 12-week old wild-type (WT and transgenic (TG R6/2 mice, an HD mouse model, and correlated these interactions with gene expression levels. At the level of the individual gene, we found decreases in the number of sites occupied by AcH3 in the TG striatum. In addition, the total number of genes bound by AcH3 was decreased. Surprisingly, the loss of AcH3 binding sites occurred within the coding regions of the genes rather than at the promoter region. We also found that the presence of AcH3 at any location within a gene strongly correlated with the presence of its transcript in both WT and TG striatum. In the TG striatum, treatment with histone deacetylase (HDAC inhibitors increased global AcH3 levels with concomitant increases in transcript levels; however, AcH3 binding at select gene loci increased only slightly. This study demonstrates that histone H3 acetylation at lysine residues 9 and 14 and active gene expression are intimately tied in the rodent brain, and that this fundamental relationship remains unchanged in an HD mouse model despite genome-wide decreases in histone H3 acetylation.

  7. Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

    OpenAIRE

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad

    2008-01-01

    Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion...

  8. Nourseothricin N-acetyl transferase: a positive selection marker for mammalian cells.

    Directory of Open Access Journals (Sweden)

    Bose S Kochupurakkal

    Full Text Available Development of Nourseothricin N-acetyl transferase (NAT as a selection marker for mammalian cells is described. Mammalian cells are acutely susceptible to Nourseothricin, similar to the widely used drug Puromycin, and NAT allows for quick and robust selection of transfected/transduced cells in the presence of Nourseothricin. NAT is compatible with other selection markers puromycin, hygromycin, neomycin, blasticidin, and is a valuable addition to the repertoire of mammalian selection markers.

  9. (4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors.

    Science.gov (United States)

    Chonan, Tomomichi; Oi, Takahiro; Yamamoto, Daisuke; Yashiro, Miyoko; Wakasugi, Daisuke; Tanaka, Hiroaki; Ohoka-Sugita, Ayumi; Io, Fusayo; Koretsune, Hiroko; Hiratate, Akira

    2009-12-01

    Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the synthesis and structure-activity relationships of a series of disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2 non-selective inhibitors.

  10. CHITOSAN SOLUTIONS WITH DIFFERENT DEGREES OF ACETYLATION AS COATING ON CUT APPLE

    OpenAIRE

    Douglas de BRITTO; Maria Fernanda dos SANTOS; Odílio Benedito Garrido ASSIS

    2012-01-01

    In this study we analyzed the protective properties of different types of chitosan on minimally processed apples, concerning water loss, surface color changes and antifungal activity. Seven different chitosanbased formulations with variable molecular weight and degrees of acetylation were prepared and used to coat sliced apples which were stored in a greenhouse at 28o C and RH 80%. The coatings, with concentration of 2.0g/L, independent of chitosan type, had no sign...

  11. PROCESS OPTIMIZATION OF TETRA ACETYL ETHYLENE DIAMINE ACTIVATED HYDROGEN PEROXIDE BLEACHING OF POPULUS NIGRA CTMP

    OpenAIRE

    Qiang Zhao; Junwen Pu; Shulei Mao; Guibo Qi

    2010-01-01

    To enhance the bleaching efficiency, the activator of tetra acetyl ethylene diamine (TAED) was used in conventional H2O2 bleaching. The H2O2/TAED bleaching system can accelerate the reaction rate and shorten bleaching time at relative low temperature, which can reduce the production cost. In this research, the process with hydrogen peroxide activated by TAED bleaching of Populus nigra chemi-thermo mechanical pulp was optimized. Suitable bleaching conditions were confirmed as follows: pulp con...

  12. ROS inhibitor N-acetyl-l-cysteine antagonizes the activity of proteasome inhibitors

    OpenAIRE

    Halasi, Marianna; Wang, Ming; Chavan, Tanmay S.; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L.

    2013-01-01

    NAC (N-acetyl-l-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H2O2. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabi...

  13. Sulphoacetaldehyde acetyltransferase yields acetyl phosphate : purification from Alcaligenes defragrans and gene clusters in taurine degradation

    OpenAIRE

    Ruff, Jürgen; Denger, Karin; Cook, Alasdair M.

    2003-01-01

    The facultatively anaerobic bacterium Alcaligenes defragrans NKNTAU was found to oxidize taurine (2-aminoethanesulphonate) with nitrate as the terminal electron acceptor. Taurine was transaminated to 2-sulphoacetaldehyde. This was not converted into sulphite and acetate by a "sulphoacetaldehyde sulpho-lyase" (EC 4.4.1.12), but into sulphite and acetyl phosphate, which was identified by three methods. The enzyme, which required the addition of phosphate, thiamin diphosphate and Mg(2+) ions for...

  14. n-Propyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside

    Directory of Open Access Journals (Sweden)

    Bettina Mönch

    2013-02-01

    Full Text Available The title compound [systematic name: (2R,3R,4S,5R,6R-2-(acetoxymethyl-6-propoxytetrahydro-2H-pyran-3,4,5-triyl triacetate], C17H26O10, was formed by a Koenigs–Knorr reaction of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide and n-propanol. The central ring adopts a chair conformation. The crystal does not contain any significant interactions such as hydrogen bonds.

  15. Efficient and reproducible synthesis of [1-{sup 11}C]acetyl chloride using the loop method

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Takuya [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Zhang, Ming-Rong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp; Ogawa, Masanao [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); SHI Accelerator Service Co. Ltd., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-8686 (Japan); Fukumura, Toshimitsu; Kato, Koichi; Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2009-02-15

    [1-{sup 11}C]Acetyl chloride ([{sup 11}C]AcCl), an important [{sup 11}C]acylating agent, was synthesized by reacting [{sup 11}C]CO{sub 2} with methylmagnesium bromide coated on the inner surface of a polyethylene loop (loop method). By optimizing the reaction conditions and synthesis parameters, [1-{sup 11}C]phenylacetate and [1-{sup 11}C]benzylacetate were produced from [{sup 11}C]AcCl in high radiochemical yield and specific activity.

  16. Histone Acetylation,VERNALIZATION INSENSITIVE 3,FLOWERING LOCUS C,and the Vernalization Response

    Institute of Scientific and Technical Information of China (English)

    Donna M.Bond; Elizabeth S.Dennis; Barry J.Pogson; E.Jean Finnegan

    2009-01-01

    The quantitative induction of VIN3 by low temperatures is required for PRC2 repression of FLC and promotion of flowering (vernalization) in Arabidopsis.Histone acetylation,a chromatin modification commonly associated with gene transcription,increased on VIN3 chromatin in two spatially and temporally distinct phases in response to low temperatures.During short-term cold exposure,histone H3 acetylation at the transcription start site rapidly increased,implying that it is required for VIN3 induction.Subsequent changes in histone H3 and H4 acetylation occurred following continued VIN3 transcription during prolonged cold exposure.Members of the SAGA-like transcriptional adaptor complex,including the histone acetyltransferase GCNS,which induces expression of the cold acclimation pathway genes,do not regulate VIN3 induction during cold exposure,indicating that the cold acclimation pathway and the cold-induction of VIN3 are regulated by different transcriptional mechanisms.Mutations in the other 11 histone acetyltransferase genes did not affect VIN3 induction.However,nicotinamide,a histone deacetylase inhibitor,induced VIN3 and altered histone acetylation at the VIN3 locus.VIN3 induction was proportional to the length of nicotinamide treatment,which was associated with an early-flowering phenotype and repression of FLC.However,unlike vernalization,the repression of FLC was independent of VIN3 activity.Nicotinamide treatment did not cause a change in the expression of any genes in the autonomous pathway or members of the PRC2 complex,the well characterized repressors of FLC.Our data suggest that FLC is repressed via a novel pathway involving the SIR2 class of histone deacetylases.

  17. Histone acetylation in the olfactory bulb of young rats facilitates aversive olfactory learning and synaptic plasticity.

    Science.gov (United States)

    Wang, Y-J; Okutani, F; Murata, Y; Taniguchi, M; Namba, T; Kaba, H

    2013-03-01

    Epigenetic mechanisms play an important role in memory formation and synaptic plasticity. Specifically, histone-associated heterochromatin undergoes changes in structure during the early stages of long-term memory formation. In keeping with the classical conditioning paradigm, young rats have been shown to exhibit aversion to an odor stimulus initially presented during foot shock. We previously showed that synaptic plasticity at the dendrodendritic synapses between mitral and granule cells in the olfactory bulb (OB) underlies this aversive olfactory learning. However, the epigenetic mechanisms involved are not well characterized. Therefore, we examined whether intrabulbar infusion of trichostatin A (TSA), a histone deacetylase inhibitor, facilitates olfactory learning in young rats. TSA infusion during odor-shock training enhanced a conditioned odor aversion in a dose-dependent manner and prolonged the learned aversion. Western blot and immunohistochemical analyses showed that the level of histone H4 acetylation significantly increased until 4 h after odor-shock training in both mitral and granule cells in the OB, whereas histone H3 acetylation returned to the control level at 2 h after the training. We also obtained evidence that TSA infusion elevated acetylation of histone H4 or H3. Furthermore, in vitro electrophysiological analysis using slices of the OB revealed that application of TSA significantly enhanced the long-term potentiation induced in synaptic transmission from mitral to granule cells at dendrodendritic synapses. Taken together, these results provide evidence that histone H4 and H3 acetylation in the OB is an epigenetic mechanism associated with aversive olfactory learning in young rats.

  18. Dual Genetic Encoding of Acetyl-lysine and Non-deacetylatable Thioacetyl-lysine Mediated by Flexizyme.

    Science.gov (United States)

    Xiong, Hai; Reynolds, Noah M; Fan, Chenguang; Englert, Markus; Hoyer, Denton; Miller, Scott J; Söll, Dieter

    2016-03-14

    Acetylation of lysine residues is an important post-translational protein modification. Lysine acetylation in histones and its crosstalk with other post-translational modifications in histone and non-histone proteins are crucial to DNA replication, DNA repair, and transcriptional regulation. We incorporated acetyl-lysine (AcK) and the non-hydrolyzable thioacetyl-lysine (ThioAcK) into full-length proteins in vitro, mediated by flexizyme. ThioAcK and AcK were site-specifically incorporated at different lysine positions into human histone H3, either individually or in pairs. We demonstrate that the thioacetyl group in histone H3 could not be removed by the histone deacetylase sirtuin type 1. This method provides a powerful tool to study protein acetylation and its role in crosstalk between post-translational modifications. PMID:26914285

  19. Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Henriksen, Peter; Wagner, Sebastian Alexander; Weinert, Brian Tate;

    2012-01-01

    Post-translational modification of proteins by lysine acetylation plays important regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a widely used unicellular eukaryotic model organism in biomedical research. S. cerevisiae contains several evolutionary conserved lysin...

  20. Prevention of enzymatic browning of postharvest longan fruit by N-acetyl-L-cysteine and 4-hexylresorcinol

    Directory of Open Access Journals (Sweden)

    Chiraporn Sodchit

    2008-01-01

    Full Text Available The effects of N-acetyl-L-cysteine and 4-hexylresorcinol on browning inhibition of postharvest longan fruits cv. Daw were studied. The fruits were dipped for 5 min 5, 25, and 45 mM N-acetyl-L-cysteine and 0.01, 0.03 and 0.05% 4- hexylresorcinol, stored at 15+2C and 85 %RH for 6 days. The results showed that N-acetyl-L-cysteine prevented pericarb browning of the fruits better than 4-hexylresorcinol, which resulted in better color values but did not significantly differ (p>0.05 among the concentrations used. Besides, the longan fruits treated with N-acetyl-L-cysteine tended to decrease disease incidence and lowered weight loss 2 compared with those treated with 4-hexylresorcinol. Neither browning inhibitor had an effect on the fall off fruits.

  1. Pharmacokinetics and acetylation of sulfamethoxazole in turbot Scophthalmus maximus after intravascular administration

    Science.gov (United States)

    Chang, Zhiqiang; Liu, Fei; Lian, Chun'ang; Zhai, Qianqian; Li, Jian

    2016-07-01

    The pharmacokinetic profiles and sulfamethoxazole (SMX) acetylation process in turbot reared at 18°C were investigated. Either SMX (parent drug) or its acetylized metabolite, N4-acetylsulfamethoxazole (AcSMX), was administered intravascularly to turbot at a dosage of 50 mg/kg BW. Serum concentrations of the parent drug and its metabolite were both measured by HPLC, and the changes in concentration over time were analyzed in two- and non-compartment models because SMX treatment produced multiple peaks. The results demonstrated that the elimination half-life of the parent drugs, SMX and AcSMX, were 159.2 and 5.9 h, respectively. The apparent volume of distribution was 0.2 and 0.8 L/kg, and the clearance was 0.038 and 0.222 L/(h·kg), for SMX and AcSMX, respectively. SMX acetylation in turbot was 2.8%, and the deacetylation of AcSMX was 0.2%. These findings may be useful in optimizing SMX dosage regimens in turbot aquaculture.

  2. Infrared spectroscopy of the acetyl cation and its protonated ketene isomer

    Science.gov (United States)

    Mosley, J. D.; Young, J. W.; Duncan, M. A.

    2014-07-01

    [C2,H3,O]+ ions are generated with a pulsed discharge in a supersonic expansion containing methyl acetate or acetone. These ions are mass selected and their infrared spectra are recorded via laser photodissociation and the method of argon tagging. Computational chemistry is employed to investigate structural isomers and their spectra. The acetyl cation (CH3CO+) is the global minimum and protonated ketene (CH2COH+) is the next lowest energy isomer (+176.2 kJ/mol). When methyl acetate is employed as the precursor, the infrared spectrum reveals that only the acetyl cation is formed. Partially resolved rotational structure reveals rotation about the C3 axis. When acetone is used as the precursor, acetyl is still the most abundant cation, but there is also a minor component of protonated ketene. Computations reveal a significant barrier to interconversion between the two isomers (+221 kJ/mol), indicating that protonated ketene must be obtained via kinetic trapping. Both isomers may be present in interstellar environments, and their implications for astrochemistry are discussed.

  3. Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network.

    Science.gov (United States)

    Kanski, Regina; Sneeboer, Marjolein A M; van Bodegraven, Emma J; Sluijs, Jacqueline A; Kropff, Wietske; Vermunt, Marit W; Creyghton, Menno P; De Filippis, Lidia; Vescovi, Angelo; Aronica, Eleonora; van Tijn, Paula; van Strien, Miriam E; Hol, Elly M

    2014-10-15

    Glial fibrillary acidic protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation also controls GFAP expression in mature astrocytes. Inhibition of histone deacetylases (HDACs) with trichostatin A or sodium butyrate reduced GFAP expression in primary human astrocytes and astrocytoma cells. Because splicing occurs co-transcriptionally, we investigated whether histone acetylation changes the ratio between the canonical isoform GFAPα and the alternative GFAPδ splice variant. We observed that decreased transcription of GFAP enhanced alternative isoform expression, as HDAC inhibition increased the GFAPδ∶GFAPα ratio. Expression of GFAPδ was dependent on the presence and binding of splicing factors of the SR protein family. Inhibition of HDAC activity also resulted in aggregation of the GFAP network, reminiscent of our previous findings of a GFAPδ-induced network collapse. Taken together, our data demonstrate that HDAC inhibition results in changes in transcription, splicing and organization of GFAP. These data imply that a tight regulation of histone acetylation in astrocytes is essential, because dysregulation of gene expression causes the aggregation of GFAP, a hallmark of human diseases like Alexander's disease.

  4. Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy

    Science.gov (United States)

    Stratton, Matthew S.; McKinsey, Timothy A.

    2016-01-01

    Acetylation of lysine residues within nucleosomal histone tails provides a crucial mechanism for epigenetic control of gene expression. Acetyl groups are coupled to lysine residues by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), which are also commonly referred to as “writers” and “erasers”, respectively. In addition to altering the electrostatic properties of histones, lysine acetylation often creates docking sites for bromodomain-containing “reader” proteins. This review focuses on epigenetic control of pulmonary hypertension (PH) and associated right ventricular (RV) cardiac hypertrophy and failure. Effects of small molecule HDAC inhibitors in pre-clinical models of PH are highlighted. Furthermore, we describe the recently discovered role of bromodomain and extraterminal (BET) reader proteins in the control of cardiac hypertrophy, and provide evidence suggesting that one member of this family, BRD4, contributes to the pathogenesis of RV failure. Together, the data suggest intriguing potential for pharmacological epigenetic therapies for the treatment of PH and right-sided heart failure. PMID:25707943

  5. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    Science.gov (United States)

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

  6. Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuan, S.F.; Byrd, J.C.; Basbaum, C.; Kim, Y.S. (Veterans Administration Medical Center, San Francisco, CA (USA))

    1989-11-15

    Specific inhibitors of the glycosylation of O-glycosidically linked glycoproteins have not previously been described. When tested for their effects on mucin glycosylation in a mucin-producing colon cancer cell line, LS174T, benzyl-, phenyl-, and p-nitrophenyl-N-acetyl-alpha-galactosaminide inhibited the formation of fully glycosylated mucin in a dose-dependent manner. Free aryl-oligosaccharides were found in the medium of treated cells labeled with ({sup 3}H)glucosamine, ({sup 3}H)galactose, ({sup 3}H)fucose, ({sup 3}H)mannosamine, or phenyl-alpha-(6-{sup 3}H) N-acetylgalactosamine. UDP-Gal:GalNAc-beta 1,3-galactosyltransferase was inhibited by aryl-N-acetyl-alpha-galactosaminides but not by a number of other aryl-glycosides. Treatment with these inhibitors also causes reversible morphologic changes including formation of intercellular cysts. Aryl-N-acetyl-alpha-galactosaminides can be useful for the structural and functional studies of mucin macromolecules and other O-linked glycoproteins.

  7. Acetylation of oil palm empty fruit bunch fiber as an adsorbent for removal of crude oil.

    Science.gov (United States)

    Asadpour, Robabeh; Sapari, Nasiman B; Isa, Mohamed Hasnain; Kakooei, Saeid

    2016-06-01

    Removal of oil spillage from the environment is a global concern. Various methods, including the use of fibers as sorbents, have been developed for oil spill control. Oil palm empty fruit bunch (OPEFB) fiber is a plant biomass that may be acetylated by acetic anhydride using N-bromosuccinimide (NBS) as a catalyst; here, the extent of acetylation may be calculated in terms of weight percent gain (WPG). The modified fiber was used to remove Tapis and Arabian crude oils. The optimum time, temperature, and catalyst concentration were 4 h, 120 °C, and 3 %, respectively, and these parameters could achieve an 11.49 % increase in WPG. The optimized parameters improved the adsorption capacity of OPEFB fibers for crude oil removal. The acetylated OPEFB fibers were characterized by using Fourier transform infrared spectroscopy and field emission scanning electron microscopy to observe the functional groups available and morphology. Kinetic and isotherm studies were conducted using different contact times and oil/water ratios. The rate of oil sorption onto the OPEFB fibers can be adequately described by the pseudo-second-order equation. Adsorption studies revealed that adsorption of crude oil on treated OPEFB fiber could be best described by the Langmuir isotherm model.

  8. VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

    Energy Technology Data Exchange (ETDEWEB)

    Bellili, A.; Hochlaf, M., E-mail: hochlaf@univ-mlv.fr, E-mail: martin.schwell@lisa.u-pec.fr [Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, Université Paris-Est, 5 bd Descartes, 77454 Marne-la-Vallée (France); Schwell, M., E-mail: hochlaf@univ-mlv.fr, E-mail: martin.schwell@lisa.u-pec.fr; Bénilan, Y.; Fray, N.; Gazeau, M.-C. [Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA), UMR 7583 CNRS, Institut Pierre et Simon Laplace, Universités Paris-Est Créteil et Paris Diderot, 61 Avenue du Général de Gaulle, 94010 Créteil (France); Mogren Al-Mogren, M. [Chemistry Department, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Guillemin, J.-C. [Institut des Sciences Chimiques de Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, Allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7 (France); Poisson, L. [Laboratoire Francis Perrin, CNRS URA 2453, CEA, IRAMIS, Laboratoire Interactions Dynamique et Lasers, Bât 522, F-91191 Gif/Yvette (France)

    2014-10-07

    The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed.

  9. Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics.

    Science.gov (United States)

    Wu, Xia; Vellaichamy, Adaikkalam; Wang, Dongping; Zamdborg, Leonid; Kelleher, Neil L; Huber, Steven C; Zhao, Youfu

    2013-02-21

    Protein lysine acetylation (LysAc) has recently been demonstrated to be widespread in E. coli and Salmonella, and to broadly regulate bacterial physiology and metabolism. However, LysAc in plant pathogenic bacteria is largely unknown. Here we first report the lysine acetylome of Erwinia amylovora, an enterobacterium causing serious fire blight disease of apples and pears. Immunoblots using generic anti-lysine acetylation antibodies demonstrated that growth conditions strongly affected the LysAc profiles in E. amylovora. Differential LysAc profiles were also observed for two E. amylovora strains, known to have differential virulence in plants, indicating translational modification of proteins may be important in determining virulence of bacterial strains. Proteomic analysis of LysAc in two E. amylovora strains identified 141 LysAc sites in 96 proteins that function in a wide range of biological pathways. Consistent with previous reports, 44% of the proteins are involved in metabolic processes, including central metabolism, lipopolysaccharide, nucleotide and amino acid metabolism. Interestingly, for the first time, several proteins involved in E. amylovora virulence, including exopolysaccharide amylovoran biosynthesis- and type III secretion-associated proteins, were found to be lysine acetylated, suggesting that LysAc may play a major role in bacterial virulence. Comparative analysis of LysAc sites in E. amylovora and E. coli further revealed the sequence and structural commonality for LysAc in the two organisms. Collectively, these results reinforce the notion that LysAc of proteins is widespread in bacterial metabolism and virulence. PMID:23234799

  10. Acetylation of oil palm empty fruit bunch fiber as an adsorbent for removal of crude oil.

    Science.gov (United States)

    Asadpour, Robabeh; Sapari, Nasiman B; Isa, Mohamed Hasnain; Kakooei, Saeid

    2016-06-01

    Removal of oil spillage from the environment is a global concern. Various methods, including the use of fibers as sorbents, have been developed for oil spill control. Oil palm empty fruit bunch (OPEFB) fiber is a plant biomass that may be acetylated by acetic anhydride using N-bromosuccinimide (NBS) as a catalyst; here, the extent of acetylation may be calculated in terms of weight percent gain (WPG). The modified fiber was used to remove Tapis and Arabian crude oils. The optimum time, temperature, and catalyst concentration were 4 h, 120 °C, and 3 %, respectively, and these parameters could achieve an 11.49 % increase in WPG. The optimized parameters improved the adsorption capacity of OPEFB fibers for crude oil removal. The acetylated OPEFB fibers were characterized by using Fourier transform infrared spectroscopy and field emission scanning electron microscopy to observe the functional groups available and morphology. Kinetic and isotherm studies were conducted using different contact times and oil/water ratios. The rate of oil sorption onto the OPEFB fibers can be adequately described by the pseudo-second-order equation. Adsorption studies revealed that adsorption of crude oil on treated OPEFB fiber could be best described by the Langmuir isotherm model. PMID:26944428

  11. Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth

    Institute of Scientific and Technical Information of China (English)

    Jin Wu; Zongli Zhou; Yinghe Hu; Suzhen Dong

    2012-01-01

    Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 (GPR41).In addition,it is an inhibitor of histone deacetylase (HDAC).Butyrate treatment results in the hyperacetylation of histones,with resultant multiple biological effects including inhibition of proliferation,induction of cell cycle arrest,and apoptosis,in a variety of cultured mammalian cells.However,it is not clear whether GPR41 is actively involved in the above-mentioned processes.In this study,we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes.We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment.Moreover,GPR41 had an inhibitory effect on the anti-proliferative,pro-apoptotic effects of butyrate.GPR41 expression induced cell cycle arrest at the Gl-stage,while its activation by butyrate can cause more cells to pass the Gl checkpoint.These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation,apoptosis,and the cell cycle.

  12. Lysine Succinylation Is a Frequently Occurring Modification in Prokaryotes and Eukaryotes and Extensively Overlaps with Acetylation

    Directory of Open Access Journals (Sweden)

    Brian T. Weinert

    2013-08-01

    Full Text Available Recent studies have shown that lysines can be posttranslationally modified by various types of acylations. However, except for acetylation, very little is known about their scope and cellular distribution. We mapped thousands of succinylation sites in bacteria (E. coli, yeast (S. cerevisiae, human (HeLa cells, and mouse liver tissue, demonstrating widespread succinylation in diverse organisms. A majority of succinylation sites in bacteria, yeast, and mouse liver were acetylated at the same position. Quantitative analysis of succinylation in yeast showed that succinylation was globally altered by growth conditions and mutations that affected succinyl-coenzyme A (succinyl-CoA metabolism in the tricarboxylic acid cycle, indicating that succinylation levels are globally affected by succinyl-CoA concentration. We preferentially detected succinylation on abundant proteins, suggesting that succinylation occurs at a low level and that many succinylation sites remain unidentified. These data provide a systems-wide view of succinylation and its dynamic regulation and show its extensive overlap with acetylation.

  13. Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics.

    Science.gov (United States)

    Bernier, Morgan; Luo, Yi; Nwokelo, Kingsley C; Goodwin, Michelle; Dreher, Sarah J; Zhang, Pei; Parthun, Mark R; Fondufe-Mittendorf, Yvonne; Ottesen, Jennifer J; Poirier, Michael G

    2015-12-09

    H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF binding. These findings show that nucleosomes remain dynamic, while H1 is bound and H1 dissociation is not required for TF binding within the nucleosome. Furthermore, our H3K56 acetylation measurements suggest that a single-histone PTM can define regions of the genome that are not regulated by H1.

  14. VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

    Science.gov (United States)

    Bellili, A.; Schwell, M.; Bénilan, Y.; Fray, N.; Gazeau, M.-C.; Mogren Al-Mogren, M.; Guillemin, J.-C.; Poisson, L.; Hochlaf, M.

    2014-10-01

    The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed.

  15. Dynamics of DNA methylation and Histone H4 acetylation during floral bud differentiation in azalea

    Directory of Open Access Journals (Sweden)

    Valledor Luis

    2010-01-01

    Full Text Available Abstract Background The ability to control the timing of flowering is a key strategy for planning production in ornamental species such as azalea, however it requires a thorough understanding of floral transition. Floral transition is achieved through a complex genetic network and regulated by multiple environmental and endogenous cues. Dynamic changes between chromatin states facilitating or inhibiting DNA transcription regulate the expression of floral induction pathways in response to environmental and developmental signals. DNA methylation and histone modifications are involved in controlling the functional state of chromatin and gene expression. Results The results of this work indicate that epigenetic mechanisms such as DNA methylation and histone H4 acetylation have opposite and particular dynamics during the transition from vegetative to reproductive development in the apical shoots of azalea. Global levels of DNA methylation and histone H4 acetylation as well as immunodetection of 5-mdC and acetylated H4, in addition to a morphological study have permitted the delimitation of four basic phases in the development of the azalea bud and allowed the identification of a stage of epigenetic reprogramming which showed a sharp decrease of whole DNA methylation similar to that is defined in other developmental processes in plants and in mammals. Conclusion The epigenetic control and reorganization of chromatin seem to be decisive for coordinating floral development in azalea. DNA methylation and H4 deacetylation act simultaneously and co-ordinately, restructuring the chromatin and regulating the gene expression during soot apical meristem development and floral differentiation.

  16. Acetylation of alcohols and phenols under solvent-free conditions using iron zirconium phosphate

    Institute of Scientific and Technical Information of China (English)

    Abdol R. Hajipour; Hirbod Karimi; Amir Masti

    2015-01-01

    Iron zirconium phosphate (ZPFe) nanoparticles were found to function as an efficient catalyst for the acetylation of a wide range of alcohols and phenols using acetic anhydride, generating good to excellent yields under solvent‐free conditions. The steric and electronic properties of various sub‐strates had a significant influence on the reaction conditions required to achieve the acetylation. The catalyst used in the current study was characterized by inductively coupled plasma‐optical emission spectrometry, X‐ray diffraction, N2 adsorption‐desorption, scanning electron microscopy, and transmission electron microscopy. These analyses revealed that the interlayer distance in the catalyst increased from 7.5 to 9.3 Å when Fe3+was intercalated between the layers, whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered and reused at least six times without any discernible decrease in its catalytic activity. This new method for the acetylation of alcohols and phenols has several important advantages, including mild and environ‐mentally friendly reaction conditions, as well as good to excellent yields and a facile work‐up.

  17. MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition.

    Science.gov (United States)

    Luo, Huacheng; Shenoy, Anitha K; Li, Xuehui; Jin, Yue; Jin, Lihua; Cai, Qingsong; Tang, Ming; Liu, Yang; Chen, Hao; Reisman, David; Wu, Lizi; Seto, Edward; Qiu, Yi; Dou, Yali; Casero, Robert A; Lu, Jianrong

    2016-06-21

    The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression. PMID:27292636

  18. MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Huacheng Luo

    2016-06-01

    Full Text Available The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression.

  19. VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

    International Nuclear Information System (INIS)

    The present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed

  20. Regulation of Histone Acetylation and Apoptosis by Trichostatin in HL-60 Cells

    Institute of Scientific and Technical Information of China (English)

    李新刚; 陈维凯; 谷俊侠; 崔国惠; 陈燕

    2004-01-01

    In order to examine the strong anticancer action and low toxicity of Trichostatin A(TSA), the effect of TSA was examined on the growth inhibition, acetylation of histone H3 and apoptosis in HL-60 cells by employing MTT, immunocytochemical techniques, and Annexin-V-FITC/PI assay. Our results showed that TSA could inhibit proliferation of HL- 60 cells in a time- and dose-dependent manner, and the IC50 at the 36th h was 100 ng/ml. The apoptosis-inducing effect of TSA on HL-60 cells was also time- and dose-dependent. But it didn't demonstrate apparent apoptosis induction in NPBMNCs within specific dose and time range. Both of the acetylation of histone H3 in HL-60 cells and NPBMNCs increased significantly (P<0.05) after treated with 100 ng/ml TSA for 4 h. However, there was no significant differences between the two groups (P>0.05). It is concluded that TSA can inhibit growth and induce apoptosis of HL-60 cells in a time- and dosedependent manner, and is able to selectively induce apoptosis in HL-60 cells but does not respond in NPBMNCs under the same conditions. The difference of TSA between HL-60 cells and NPBMNCs can't be explained by the regulation of histone acetylation.

  1. Reversible Histone Acetylation Involved in Transcriptional Regulation of WT1 Gene

    Institute of Scientific and Technical Information of China (English)

    Yangguang SHAO; Jun LU; Cao CHENG; Liguo CUI; Guoping ZHANG; Baiqu HUANG

    2007-01-01

    To validate the involvement of reversible histone acetylation in the transcriptional regulation of human Wilms' tumor 1 gene (WT1), we analyzed the roles of histone deacetylases (HDACs) and histone acetyltransferase in this epigenetic process. Of the six HDACs (HDAC1-6) examined, HDAC4 and HDAC5 were found to have significant repressing effects on the activity of the WT1 reporter gene, as revealed by luciferase reporter assays and quantitative real-time reverse transcription-polymerase chain reaction assays.Luciferase reporter assays showed that the histone acetyltransferase p300 was able to counteract the HDAC4/HDAC5-mediated repression and that p300/CBP synergized with transcription factors Sp1, c-Myb, and Ets-1 in activation of the WT1 reporter. Chromatin immunoprecipitation experiments showed that p300 promotes the acetylation level of histone H3 at the WT1 intronic enhancer. Based on these data, we proposed a hypothetical model for the involvement of reversible histone acetylation in transcriptional regulation of the WT1 gene. This study provides further insight into the mechanisms of transcriptional regulation of the WT1 gene and WT1-associated diseases treatment.

  2. 2-Aminofluorene metabolism and DNA adduct formation by mononuclear leukocytes from rapid and slow acetylator mouse strains.

    Science.gov (United States)

    Levy, G N; Chung, J G; Weber, W W

    1994-02-01

    Following exposure of mice to the arylamine carcinogen 2-aminofluorene, DNA-carcinogen adducts can be found in the target tissues liver and bladder, and also in circulating leukocytes. Evidence is presented here that mouse mononuclear leukocytes (MNL) are capable of metabolizing 2-aminofluorene to DNA-binding metabolites which give rise to the adducts found in the MNL. Both lymphocytes and monocytes were able to acetylate arylamines during 18 h of culture. The degree of acetylation was determined by the N-acetyltransferase genotype of the mice as shown through use of acetylator congenic strains which differ only in the Nat-2 gene. Cultured MNL from rapid acetylator mice (C57BL/6J and A.B6-Natr) produced about twice as much N-acetylaminofluorene from 2-aminofluorene and 6- to 8-fold as much N-acetyl-p-aminobenzoic acid from p-aminobenzoic acid as cells from slow acetylator mice (B6.A-Nat(s) and A/J). Other differences in arylamine metabolism by MNL in culture were observed and shown to be due to genetic factors, currently unidentified, other than N-acetyltransferase. DNA adduct formation following incubation of MNL with the arylamine carcinogen 2-aminofluorene was related to both acetylation capacity and to other genetic metabolic factors in the mouse genome. MNL from rapid acetylator mice with the C57BL/6J background (B6) had 3-fold the DNA adduct levels of cells from the corresponding slow acetylator congenic (B6.A-Nat(s)). Similarly, MNL from rapid acetylator mice with the A/J background (A.B6-Natr) had twice the DNA adduct levels of those from their corresponding slow congenic (A). Adduct levels in MNL from C57BL/6J were nearly the same as those of MNL from A/J, again indicating the involvement of loci other than acetylation in DNA adduct formation. The finding of genetically dependent arylamine carcinogen metabolism and DNA adduct formation in cultured MNL suggests the possibility of using cultured MNL for assessing individual susceptibility to arylamine

  3. Activation of the aryl hydrocarbon receptor by carcinogenic aromatic amines and modulatory effects of their N-acetylated metabolites.

    Science.gov (United States)

    Juricek, Ludmila; Bui, Linh-Chi; Busi, Florent; Pierre, Stéphane; Guyot, Erwan; Lamouri, Aazdine; Dupret, Jean-Marie; Barouki, Robert; Coumoul, Xavier; Rodrigues-Lima, Fernando

    2015-12-01

    Aromatic amines (AAs) are an important class of chemicals which account for 12 % of known carcinogens. The biological effects of AAs depend mainly on their biotransformation into reactive metabolites or into N-acetylated metabolites which are generally considered as less toxic. Although the activation of the aryl hydrocarbon receptor (AhR) pathway by certain carcinogenic AAs has been reported, the effects of their N-acetylated metabolites on the AhR have not been addressed. Here, we investigated whether carcinogenic AAs and their N-acetylated metabolites may activate/modulate the AhR pathway in the absence and/or the presence of a bona fide AhR ligand (benzo[a]pyrene/B(a)P]. In agreement with previous studies, we found that certain AAs activated the AhR in human liver and lung cells as assessed by an increase in cytochrome P450 1A1 (CYP1A1) expression and activity. Altogether, we report for the first time that these properties can be modulated by the N-acetylation status of the AA. Whereas 2-naphthylamine significantly activated the AhR and induced CYP1A1 expression, its N-acetylated metabolite was less efficient. In contrast, the N-acetylated metabolite of 2-aminofluorene was able to significantly activate AhR, whereas the parent AA, 2-aminofluorene, did not. In the presence of B(a)P, activation of AhR or antagonist effects were observed depending on the AA or its N-acetylated metabolite. Activation and/or modulation of the AhR pathway by AAs and their N-acetylated metabolites may represent a novel mechanism contributing to the toxicological effects of AAs. More broadly, our data suggest biological interactions between AAs and other classes of xenobiotics through the AhR pathway. PMID:25224404

  4. Mass Transfer and Chemical Reaction Approach of the Kinetics of the Acetylation of Gadung Flour using Glacial Acetic Acid

    Directory of Open Access Journals (Sweden)

    Andri Cahyo Kumoro

    2015-03-01

    Full Text Available Acetylation is one of the common methods of modifying starch properties by introducing acetil (CH3CO groups to starch molecules at low temperatures. While most acetylation is conducted using starch as anhidroglucose source and acetic anhydride or vinyl acetate as nucleophilic agents, this work employ reactants, namely flour and glacial acetic acid. The purpose of this work are to study the effect of pH reaction and GAA/GF mass ratio on the rate of acetylation reaction and to determine its rate constants. The acetylation of gadung flour with glacial acetic acid in the presence of sodium hydroxide as a homogenous catalyst was studied at ambient temperature with pH ranging from 8-10 and different mass ratio of acetic acid : gadung flour (1:3; 1:4; and 1:5. It was found that increasing pH, lead to increase the degree of substitution, while increasing GAA/GF mass ratio caused such decreases in the degree of substitution, due to the hydrolysis of the acetylated starch. The desired starch acetylation reaction is accompanied by undesirable hydrolysis reaction of the acetylated starch after 40-50 minutes reaction time. Investigation of kinetics of the reaction observed that the value of mass transfer rate constant (Kcs is smaller than the surface reaction rate constant (k. Thus, it can be concluded that rate controlling step is mass transfer.  © 2015 BCREC UNDIP. All rights reservedReceived: 7th August 2014; Revised: 8th September 2014; Accepted: 14th September 2014How to Cite: Kumoro, A.C., Amelia, R. (2015. Mass Transfer and Chemical Reaction Approach of the Kinetics of the Acetylation of Gadung Flour using Glacial Acetic Acid. Bulletin of Chemical Reaction Engineering & Catalysis, 10 (1: 30-37. (doi:10.9767/bcrec.10.1.7181.30-37Permalink/DOI: http://dx.doi.org/10.9767/bcrec.10.1.7181.30-37

  5. Comparison of Catalysts Preyssler and Silica-Supported Nano Preyssler in the Synthesis of Acetyl Salicylic Acid

    OpenAIRE

    Nazari, H.; A. Ahmadpour; Bamoharram, F. F.; M. M. Heravi; Eslami, N.

    2012-01-01

    The extensive demand for cleaner environment is forcing chemical industry to use less hazardous materials. In this regard, heteropolyacids attracted considerable amount of interest due to the less toxic behavior in addition of possessing higher acidity. Heteropoly acids have been used as catalysts for the reaction of salicylic acid with acetic anhydride. The performance of different forms of heteropoly acids in the presence of acetic anhydride as acetylating agent for acetylation of salicylic...

  6. Synthesis of spiro[indolo-1,5-benzodiazepines] from 3-acetyl coumarins for use as possible antianxiety agents

    Indian Academy of Sciences (India)

    Raviraj A Kusanur; Manjunath Ghate; Manohar V Kulkarni

    2004-08-01

    3-Acetyl coumarins (1) when allowed react with isatin (2) gave corresponding 3-(3'-hydroxy-2'-oxo indolo) acetyl coumarins (3), which on dehydration afforded the corresponding ,-unsaturated ketones (4). Cyclocondensation of (4) with substituted -phenylene diamines resulted in novel 3-coumarinyl spiro[indolo-1,5-benzodiazepines] (5). Structures of all the compounds have been established on the basis of their IR, NMR and mass spectral data and have been screened for their antimicrobial activity and antianxiety activity in mice.

  7. Fate of the fragrance material acetyl cedrene in sediment inhabited by the benthic molluscs Macoma balthica and Mya arenaria

    OpenAIRE

    Baral, Kaushal; Burdukovska, Valentina; David, Minodora; Kærhus Olufsen, Mads

    2013-01-01

    In recent time it has come to concern that hydrophobic organic compounds, from the relatively large group of fragrance materials, enter the aquatic environment via drainage systems and bioaccumulate in the sediment and biota. Acetyl cedrene is one of these compounds. In this report the fate and effects of acetyl cedrene were studied on two species of marine molluscs – Macoma balthica and Mya arenaria – with different feeding strategies. An experiment was conducted over a period of 14 days, af...

  8. Catalytic and glycan-binding abilities of ppGalNAc-T2 are regulated by acetylation

    DEFF Research Database (Denmark)

    Zlocowski, Natacha; Sendra, Victor G; Lorenz, Virginia;

    2011-01-01

    Post-translational acetylation is an important molecular regulatory mechanism affecting the biological activity of proteins. Polypeptide GalNAc transferases (ppGalNAc-Ts) are a family of enzymes that catalyze initiation of mucin-type O-glycosylation. All ppGalNAc-Ts in mammals are type II...... of the R-type lectin domain of ppGalNAc-T2. Acetylation effect on ppGalNAc-T2 biological activity in vitro was studied using a purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363, S373, K521, and S529......); the first five are located in the catalytic domain. Specific glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The last two amino acids, K521 and S529, are located in the lectin domain, and their acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2...

  9. Rewiring AMPK and mitochondrial retrograde signaling for metabolic control of aging and histone acetylation in respiratory-defective cells.

    Science.gov (United States)

    Friis, R Magnus N; Glaves, John Paul; Huan, Tao; Li, Liang; Sykes, Brian D; Schultz, Michael C

    2014-04-24

    Abnormal respiratory metabolism plays a role in numerous human disorders. We find that regulation of overall histone acetylation is perturbed in respiratory-incompetent (ρ(0)) yeast. Because histone acetylation is highly sensitive to acetyl-coenzyme A (acetyl-CoA) availability, we sought interventions that suppress this ρ(0) phenotype through reprogramming metabolism. Nutritional intervention studies led to the discovery that genetic coactivation of the mitochondrion-to-nucleus retrograde (RTG) response and the AMPK (Snf1) pathway prevents abnormal histone deacetylation in ρ(0) cells. Metabolic profiling of signaling mutants uncovered links between chromatin-dependent phenotypes of ρ(0) cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation reprograms energy metabolism to increase the supply of acetyl-CoA to lysine acetyltransferases and extend the chronological lifespan of ρ(0) cells. Our results strengthen the framework for rational design of nutrient supplementation schemes and drug-discovery initiatives aimed at mimicking the therapeutic benefits of dietary interventions.

  10. Rewiring AMPK and Mitochondrial Retrograde Signaling for Metabolic Control of Aging and Histone Acetylation in Respiratory-Defective Cells

    Directory of Open Access Journals (Sweden)

    R. Magnus N. Friis

    2014-04-01

    Full Text Available Abnormal respiratory metabolism plays a role in numerous human disorders. We find that regulation of overall histone acetylation is perturbed in respiratory-incompetent (ρ0 yeast. Because histone acetylation is highly sensitive to acetyl-coenzyme A (acetyl-CoA availability, we sought interventions that suppress this ρ0 phenotype through reprogramming metabolism. Nutritional intervention studies led to the discovery that genetic coactivation of the mitochondrion-to-nucleus retrograde (RTG response and the AMPK (Snf1 pathway prevents abnormal histone deacetylation in ρ0 cells. Metabolic profiling of signaling mutants uncovered links between chromatin-dependent phenotypes of ρ0 cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation reprograms energy metabolism to increase the supply of acetyl-CoA to lysine acetyltransferases and extend the chronological lifespan of ρ0 cells. Our results strengthen the framework for rational design of nutrient supplementation schemes and drug-discovery initiatives aimed at mimicking the therapeutic benefits of dietary interventions.

  11. Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57

    Science.gov (United States)

    Hsu, Chun-Ru; Liao, Chun-Hsing; Lin, Tzu-Lung; Yang, Han-Ru; Yang, Feng-Ling; Hsieh, Pei-Fang; Wu, Shih-Hsiung; Wang, Jin-Town

    2016-01-01

    Klebsiella pneumoniae can cause community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) is important for its virulence. Among 79 capsular (K) types discovered thus far, K57 is often associated with PLA. Here, we report the identification of a K57 variant. Cps gene locus sequencing revealed differences between the K57 reference strain 4425/51 (Ref-K57) and a variant, the PLA isolate A1142. While Ref-K57 cps contained orf13 encoding a putative acetyltransferase, the insertion of a putative transposase-encoding gene at this position was detected in A1142. This variation was detected in other K57 clinical strains. Biochemical analyses indicated that A1142 was deficient in CPS acetylation. Genetic replacement and complementation verified that orf13 was responsible for CPS acetylation. Acetylation increased CPS immunoreactivity to antiserum and enhanced K. pneumoniae induction of pro-inflammatory cytokines through JNK and MAPK signaling. While acetylation diminished the serum resistance of bacteria, it promoted adhesion to intestinal epithelial cells possibly via increasing production of type I fimbriae. In conclusion, acetylation-mediated capsular variation in K57 was observed. Capsular acetylation contributed to the variety and antigenic diversity of CPS, influenced its biological activities, and was involved in K. pneumoniae-host interactions. These findings have implications for vaccine design and pathogenicity of K. pneumoniae. PMID:27550826

  12. Accurate in silico identification of species-specific acetylation sites by integrating protein sequence-derived and functional features

    Science.gov (United States)

    Li, Yuan; Wang, Mingjun; Wang, Huilin; Tan, Hao; Zhang, Ziding; Webb, Geoffrey I.; Song, Jiangning

    2014-07-01

    Lysine acetylation is a reversible post-translational modification, playing an important role in cytokine signaling, transcriptional regulation, and apoptosis. To fully understand acetylation mechanisms, identification of substrates and specific acetylation sites is crucial. Experimental identification is often time-consuming and expensive. Alternative bioinformatics methods are cost-effective and can be used in a high-throughput manner to generate relatively precise predictions. Here we develop a method termed as SSPKA for species-specific lysine acetylation prediction, using random forest classifiers that combine sequence-derived and functional features with two-step feature selection. Feature importance analysis indicates functional features, applied for lysine acetylation site prediction for the first time, significantly improve the predictive performance. We apply the SSPKA model to screen the entire human proteome and identify many high-confidence putative substrates that are not previously identified. The results along with the implemented Java tool, serve as useful resources to elucidate the mechanism of lysine acetylation and facilitate hypothesis-driven experimental design and validation.

  13. What a Role did Histidine Residue Play in Arylamine N-Acetyltransferase 2 Acetylation? A Quantum Chemistry Study

    Institute of Scientific and Technical Information of China (English)

    QIAO Qing-An; CAI Zheng-Ting; YANG Chuan-Lu; WANG Mei-Shan

    2006-01-01

    Arylamine N-acetyltransferases (NATs, EC 2.3.1.5) catalyze an acetyl group transfer from acetyl coenzyme A (AcCoA) to primary arylamines and play a very important role in the metabolism and bioactivation of drugs and carcinogens. Experiments revealed that His-107 was likely the residues responsible for mediating acetyl transfer.The full catalytic mechanism of acetylation process has been examined by density functional theory. The results indicate that, if the acetyl group is directly transferred from the donor, p-nitrophenyl acetate, to the acceptor, cysteine,the high activation energy will be a great hindrance. These energies have dropped in a little range of 20-25 k J/mol when His-107 assisted the transfer process. However, when protonated His-107 mediated the reaction, the activation energies have been dropped about 73-85 kJ/mol. Our calculations strongly supported an enzyme acetylation mechanism that experiences a thiolate-imidazolium pair, and verified the presumption from experiments.

  14. Interactions between N-acetyl-L-cysteine protected CdTe quantum dots and doxorubicin through spectroscopic method

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiupei, E-mail: xiupeiyang@163.com [Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, Nanchong 637000 (China); College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China); Lin, Jia; Liao, Xiulin; Zong, Yingying; Gao, Huanhuan [College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000 (China)

    2015-06-15

    Highlights: • CdTe quantum dots with the diameter of 3–5 nm were synthesized in aqueous solution. • The modified CdTe quantum dots showed well fluorescence properties. • The interaction between the CdTe quantum dots and doxorubicin (DR) was investigated. - Abstract: N-acetyl-L-cysteine protected cadmium telluride quantum dots with a diameter of 3–5 nm were synthesized in aqueous solution. The interaction between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin was investigated by ultraviolet–visible absorption and fluorescence spectroscopy at physiological conditions (pH 7.2, 37 °C). The results indicate that electron transfer has occurred between N-acetyl-L-cysteine/cadmium telluride quantum dots and doxorubicin under light illumination. The quantum dots react readily with doxorubicin to form a N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex via electrostatic attraction between the −NH{sub 3}{sup +} moiety of doxorubicin and the −COO{sup −} moiety of N-acetyl-L-cysteine/cadmium telluride quantum dots. The interaction of N-acetyl-L-cysteine/cadmium telluride-quantum dots/doxorubicin complex with bovine serum albumin was studied as well, showing that the complex might induce the conformation change of bovine serum due to changes in microenvironment of bovine serum.

  15. EFFECTS OF CURCUMIN ON PROLIFERATION OF NB4 CELLS AND ACETYLATION OF HISTONE H3 AND P53

    Institute of Scientific and Technical Information of China (English)

    陈燕; 李新刚; 吴青

    2004-01-01

    Objective: To investigate the effects of curcumin on the proliferation of NB4 cells and the acetylation of histone H3 and no-histone p53. Methods: NB4 cells were cultured and treated with or without curcumin at different concentration (50 (mol/L, 25(mol/L, 12.5(mol/L, 6.25(mol/L, 3.125(mol/L) at various time points (oh, 4h, 8h, 12h, 24h). Western blot analysis was performed to determine the level of acetylated histone H3, p53 and acetylated p53, MTT assay was performed to examine the proliferation of NB4 cells. Results: the proliferation of NB4 cells was inhibited by curcumin in a time- and dose-dependent manner, the IC50 at 24h and 36h were 40(mol/L and 25(mol/L respectively. The levels of acetylated histone H3 and acetylated p53 were increased obviously. Conclusion: curcumin possessed the founction of deacetylases inhibitor, increased the level of acetylated histone H3 and the expression of tumor suppressor p53, enhanced later's activity, and inhibited the proliferation of NB4 cell.

  16. Sources, Sinks and Cycling of Acetyl Radicals in Tobacco Smoke: A Model for Biomass Burning Chemistry

    Science.gov (United States)

    Hu, N.; Green, S. A.

    2012-12-01

    Smoke near the source of biomass burning contains high concentrations of reactive compounds, with NO and CH3CHO concentrations four to six orders of magnitude higher than those in the ambient atmosphere. Tobacco smoke represents a special case of biomass burning that is quite reproducible in the lab and may elucidate early processes in smoke from other sources. The origins, identities, and reactions of radical species in tobacco smoke are not well understood, despite decades of study on the concentrations and toxicities of the relatively stable compounds in smoke. We propose that reactions of NO2 and aldehydes are a primary source for transient free radicals in tobacco smoke, which contrasts with the long-surmised mechanism of reaction between NO2 and dienes. The objective of this study was to investigate the sources, sinks and cycling of acetyl radical in tobacco smoke. Experimentally, the production of acetyl radical was demonstrated both in tobacco smoke and in a simplified mixture of air combined with NO and acetaldehyde, both of which are significant components of smoke. Acetyl radicals were trapped from the gas phase using 3-amino-2, 2, 5, 5-tetramethyl-proxyl (3AP) on solid support to form stable 3AP adducts for later analysis by high performance liquid chromatography (HPLC), mass spectrometry/tandem mass spectrometry (MS-MS/MS) and liquid chromatography-mass spectrometry (LC-MS). The dynamic nature of radical cycling in smoke makes it impossible to define a fixed concentration of radical species; 2.15×e13-3.18×e14 molecules/cm3 of acetyl radicals were measured from different cigarette samples and smoking conditions. Matlab was employed to simulate reactions of NO, NO2, O2, and a simplified set of organic compounds known to be present in smoke, with a special emphasis on acetaldehyde and the acetyl radical. The NO2/acetaldehyde mechanism initiates a cascade of chain reactions, which accounts for the most prevalent known carbon-centered radicals found in

  17. N-acetylation and phosphorylation of Sec complex subunits in the ER membrane

    Directory of Open Access Journals (Sweden)

    Soromani Christina

    2012-12-01

    Full Text Available Abstract Background Covalent modifications of proteins provide a mechanism to control protein function. Here, we have investigated modifications of the heptameric Sec complex which is responsible for post-translational protein import into the endoplasmic reticulum (ER. It consists of the Sec61 complex (Sec61p, Sbh1p, Sss1p which on its own mediates cotranslational protein import into the ER and the Sec63 complex (Sec63p, Sec62p, Sec71p, Sec72p. Little is known about the biogenesis and regulation of individual Sec complex subunits. Results We show that Sbh1p when it is part of the Sec61 complex is phosphorylated on T5 which is flanked by proline residues. The phosphorylation site is conserved in mammalian Sec61ß, but only partially in birds, and not in other vertebrates or unicellular eukaryotes, suggesting convergent evolution. Mutation of T5 to A did not affect the ability of mutant Sbh1p to complement the growth defect in a Δsbh1Δsbh2 strain, and did not result in a hypophosphorylated protein which shows that alternate sites can be used by the T5 kinase. A survey of yeast phosphoproteome data shows that Sbh1p can be phosphorylated on multiple sites which are organized in two patches, one at the N-terminus of its cytosolic domain, the other proximal to the transmembrane domain. Surprisingly, although N-acetylation has been shown to interfere with ER targeting, we found that both Sbh1p and Sec62p are cotranslationally N-acetylated by NatA, and N-acetyl-proteome data indicate that Sec61p is modified by the same enzyme. Mutation of the N-acetylation site, however, did not affect Sec62p function in posttranslational protein import into the ER. Disabling NatA resulted in growth retardation, but not in co- or posttranslational translocation defects or instability of Sec62p or Sbh1p. Conclusions We conclude that N-acetylation of transmembrane and tail-anchored proteins does not interfere with their ER-targeting, and that Sbh1p phosphorylation on T5

  18. Identification and analysis of the acetylated status of poplar proteins reveals analogous N-terminal protein processing mechanisms with other eukaryotes.

    Directory of Open Access Journals (Sweden)

    Chang-Cai Liu

    Full Text Available BACKGROUND: The N-terminal protein processing mechanism (NPM including N-terminal Met excision (NME and N-terminal acetylation (N(α-acetylation represents a common protein co-translational process of some eukaryotes. However, this NPM occurred in woody plants yet remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To reveal the NPM in poplar, we investigated the N(α-acetylation status of poplar proteins during dormancy by combining tandem mass spectrometry with TiO2 enrichment of acetylated peptides. We identified 58 N-terminally acetylated (N(α-acetylated proteins. Most proteins (47, >81% are subjected to N(α-acetylation following the N-terminal removal of Met, indicating that N(α-acetylation and NME represent a common NPM of poplar proteins. Furthermore, we confirm that poplar shares the analogous NME and N(α-acetylation (NPM to other eukaryotes according to analysis of N-terminal features of these acetylated proteins combined with genome-wide identification of the involving methionine aminopeptidases (MAPs and N-terminal acetyltransferase (Nat enzymes in poplar. The N(α-acetylated reactions and the involving enzymes of these poplar proteins are also identified based on those of yeast and human, as well as the subcellular location information of these poplar proteins. CONCLUSIONS/SIGNIFICANCE: This study represents the first extensive investigation of N(α-acetylation events in woody plants, the results of which will provide useful resources for future unraveling the regulatory mechanisms of N(α-acetylation of proteins in poplar.

  19. N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.

    Science.gov (United States)

    Günther, Lisa; Beck, Roswitha; Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

    2015-01-01

    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus. PMID:25803613

  20. The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences.

    Science.gov (United States)

    Golka, Klaus; Prior, Verena; Blaszkewicz, Meinolf; Bolt, Hermann M

    2002-03-10

    Human bladder cancer may be caused by exposure to aromatic amines. The polymorphic enzyme N-acetyltransferase 2 (NAT2) is involved in the metabolism of these compounds. Two classical studies on chemical workers in Europe, exposed in the past to aromatic amines like benzidine, unambiguously showed that the slow acetylator status is a genetic risk factor for arylamine-induced bladder cancer. In the former benzidine industry in Huddington, Great Britain, 22 of 23 exposed cases with bladder cancer, but only 57% of 95 local controls without bladder cancer were of the slow acetylator phenotype. In Leverkusen, Germany, 82% of 92 benzidine-exposed chemical workers with bladder cancer were of the slow acetylator phenotype, whereas only 48% of 331 chemical workers who had worked at that plant were of the slow acetylator phenotype. This is in line with several smaller studies, which also show an over-representation of the slow acetylator status in formerly arylamine-exposed subjects with bladder cancer. Some of these studies included also subjects that were exposed to aromatic amines by having applied dyes, paints and varnishes. These European findings are in contrast to a large study on Chinese workers occupationally exposed to aromatic amines. In this study, only five of 38 bladder cancer cases occupationally exposed to arylamines were of the slow acetylator genotype. This is much lower than the ratio of slow acetylators to the general population in China. This points to different mechanisms of susceptibility for bladder cancer upon exposure to aromatic amines between European (Caucasian) and Chinese populations.

  1. Evaluation of gels obtained from acetylation of chitosan in heterogeneous medium; Avaliacao de geis obtidos a partir da acetilacao da quitosana em meio heterogeneo

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Rosangela Balaban; Silva, Dayse Luzia Pinheiro da; Costa, Marta [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Quimica]. E-mail: balaban@digi.com.br; Raffin, Fernanda Nervo [Universidade Federal do Rio Grande do Norte (UFRGN), Natal, RN (Brazil). Centro de Ciencias da Saude. Dept. de Quimica, Tecnologia Farmaceutica e de Alimentos; Ruiz, Naira Machado da Silva [Centro de Pesquisa Leopoldo A. Miguez de Mello (CENPES), Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Chitosan was acetylated during 2, 5 and 10 h and physical gels were obtained at different polymer concentrations in N,N-dimethylacetamide containing 5% of LiCl. Acetylation was confirmed by infrared spectroscopy and {sup 13}C NMR, and degrees of acetylation in the range of 0.82-0.91 were determined by NMR. The O-acetylation degree (0.12-0.15) was exclusively determined by a volumetric method. Rheological studies showed that the storage modulus values were smaller for the more acetylated samples and increased with the temperature and the polymer concentration. All the gels presented storage modulus superior to loss modulus, evidencing more elastic than viscous characteristics. The results obtained in this work suggest a gelation process based on a balance between O and N-acetylation and intermolecular bonds. (author)

  2. Acetylation of retinal histones in diabetes increases inflammatory proteins: effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC).

    Science.gov (United States)

    Kadiyala, Chandra Sekhar Rao; Zheng, Ling; Du, Yunpeng; Yohannes, Elizabeth; Kao, Hung-Ying; Miyagi, Masaru; Kern, Timothy S

    2012-07-27

    Histone acetylation was significantly increased in retinas from diabetic rats, and this acetylation was inhibited in diabetics treated with minocycline, a drug known to inhibit early diabetic retinopathy in animals. Histone acetylation and expression of inflammatory proteins that have been implicated in the pathogenesis of diabetic retinopathy were increased likewise in cultured retinal Müller glia grown in a diabetes-like concentration of glucose. Both the acetylation and induction of the inflammatory proteins in elevated glucose levels were significantly inhibited by inhibitors of histone acetyltransferase (garcinol and antisense against the histone acetylase, p300) or activators of histone deacetylase (theophylline and resveratrol) and were increased by the histone deacetylase inhibitor, suberolylanilide hydroxamic acid. We conclude that hyperglycemia causes acetylation of retinal histones (and probably other proteins) and that the acetylation contributes to the hyperglycemia-induced up-regulation of proinflammatory proteins and thereby to the development of diabetic retinopathy.

  3. Structure Elucidation of New Acetylated Saponins, Lessoniosides A, B, C, D, and E, and Non-Acetylated Saponins, Lessoniosides F and G, from the Viscera of the Sea Cucumber Holothuria lessoni

    Directory of Open Access Journals (Sweden)

    Yadollah Bahrami

    2015-01-01

    Full Text Available Sea cucumbers produce numerous compounds with a wide range of chemical structural diversity. Among these, saponins are the most diverse and include sulfated, non-sulfated, acetylated and methylated congeners with different aglycone and sugar moieties. In this study, MALDI and ESI tandem mass spectrometry, in the positive ion mode, were used to elucidate the structure of new saponins extracted from the viscera of H. lessoni. Fragmentation of the aglycone provided structural information on the presence of the acetyl group. The presence of the O-acetyl group was confirmed by observing the mass transition of 60 u corresponding to the loss of a molecule of acetic acid. Ion fingerprints from the glycosidic cleavage provided information on the mass of the aglycone (core, and the sequence and type of monosaccharides that constitute the sugar moiety. The tandem mass spectra of the saponin precursor ions [M + Na]+ provided a wealth of detailed structural information on the glycosidic bond cleavages. As a result, and in conjunction with existing literature, we characterized the structure of five new acetylated saponins, Lessoniosides A–E, along with two non-acetylated saponins Lessoniosides F and G at m/z 1477.7, which are promising candidates for future drug development. The presented strategy allows a rapid, reliable and complete analysis of native saponins.

  4. Acetyl-L-carnitine improves behavior and dendritic morphology in a mouse model of Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Laura R Schaevitz

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder affecting 1 in 10,000 girls. Approximately 90% of cases are caused by spontaneous mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2. Girls with RTT suffer from severe motor, respiratory, cognitive and social abnormalities attributed to early deficits in synaptic connectivity which manifest in the adult as a myriad of physiological and anatomical abnormalities including, but not limited to, dimished dendritic complexity. Supplementation with acetyl-L-carnitine (ALC, an acetyl group donor, ameliorates motor and cognitive deficits in other disease models through a variety of mechanisms including altering patterns of histone acetylation resulting in changes in gene expression, and stimulating biosynthetic pathways such as acetylcholine. We hypothesized ALC treatment during critical periods in cortical development would promote normal synaptic maturation, and continuing treatment would improve behavioral deficits in the Mecp2(1lox mouse model of RTT. In this study, wildtype and Mecp2(1lox mutant mice received daily injections of ALC from birth until death (postnatal day 47. General health, motor, respiratory, and cognitive functions were assessed at several time points during symptom progression. ALC improved weight gain, grip strength, activity levels, prevented metabolic abnormalities and modestly improved cognitive function in Mecp2 null mice early in the course of treatment, but did not significantly improve motor or cognitive functions assessed later in life. ALC treatment from birth was associated with an almost complete rescue of hippocampal dendritic morphology abnormalities with no discernable side effects in the mutant mice. Therefore, ALC appears to be a promising therapeutic approach to treating early RTT symptoms and may be useful in combination with other therapies.

  5. N-Acetyl glycals are tight-binding and environmentally insensitive inhibitors of hexosaminidases.

    Science.gov (United States)

    Santana, A G; Vadlamani, G; Mark, B L; Withers, S G

    2016-06-28

    Mono-, di- and trisaccharide derivatives of 1,2-unsaturated N-acetyl-d-glucal have been synthesized and shown to function as tight-binding inhibitors/slow substrates of representative hexosaminidases. Turnover is slow and not observed in the thioamide analogue, allowing determination of the 3-dimensional structure of the complex. Inhibition is insensitive to pH and to mutation of key catalytic residues, consistent with the uncharged character of the inhibitor. These properties could render this inhibitor class less prone to development of resistance. PMID:27253678

  6. MRG15 activates the cdc2 promoter via histone acetylation in human cells

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    Pena, AndreAna N., E-mail: andreana.pena@gmail.com [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Tominaga, Kaoru; Pereira-Smith, Olivia M. [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2011-07-01

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  7. Wheat cytosolic acetyl-CoA carboxylase complements an ACC1 null mutation in yeast

    OpenAIRE

    Joachimiak, M.; Tevzadze, G.; Podkowinski, J; Haselkorn, R.; Gornicki, P.

    1997-01-01

    Spores harboring an ACC1 deletion derived from a diploid Saccharomyces cerevisiae strain, in which one copy of the entire ACC1 gene is replaced with a LEU2 cassette, fail to grow. A chimeric gene consisting of the yeast GAL10 promoter, yeast ACC1 leader, wheat cytosolic acetyl-CoA carboxylase (ACCase) cDNA, and yeast ACC1 3′ tail was used to complement a yeast ACC1 mutation. The complementation demonstrates that active wheat ACCase can be produced in yeast. At low concentrations of galactose,...

  8. Yeast Enhancer of Polycomb defines global Esa1-dependent acetylation of chromatin

    OpenAIRE

    Boudreault, Alexandre A.; Cronier, Dominique; Selleck, William; Lacoste, Nicolas; Utley, Rhea T.; Allard, Stéphane; Savard, Julie; Lane, William S.; Tan, Song; Côté, Jacques

    2003-01-01

    Drosophila Enhancer of Polycomb, E(Pc), is a suppressor of position-effect variegation and an enhancer of both Polycomb and trithorax mutations. A homologous yeast protein, Epl1, is a subunit of the NuA4 histone acetyltransferase complex. Epl1 depletion causes cells to accumulate in G2/M and global loss of acetylated histones H4 and H2A. In relation to the Drosophila protein, mutation of Epl1 suppresses gene silencing by telomere position effect. Epl1 protein is found ...

  9. Focus on acetylation: the role of histone deacetylase inhibitors in cancer therapy and beyond.

    Science.gov (United States)

    Konstantinopoulos, Panagiotis A; Karamouzis, Michalis V; Papavassiliou, Athanasios G

    2007-05-01

    Reversal of tumorigenic epigenetic alterations is an exciting strategy for anticancer drug development. Pharmacologic inhibition of histone deacetylases (HDACs) induces differentiation, proliferation arrest and apoptosis of cancer cells. In addition to their effects on histones, HDAC inhibitors increase the acetylation level of several non-histone proteins, such as transcription factors, cytoskeletal proteins and molecular chaperones, which are crucial in tumorigenesis. Most importantly, the therapeutic potential of HDAC inhibitors goes well beyond carcinogenesis and may include neurodegenerative and inflammatory disorders. This editorial discusses the implication of HDACs in carcinogenesis, the molecular basis of the selectivity of HDAC inhibitors and their possible therapeutic role in non-malignant pathologic conditions.

  10. Ras protein participated in histone acetylation-mediated cell cycle control in Physarum polycephalum

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoxue; LU Jun; ZHAO Yanmei; WANG Xiuli; HUANG Baiqu

    2005-01-01

    In this paper, we demonstrate that in Physarum polycephalum, a naturally synchronized slime mold, histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), arrestes the cell cycle at the checkpoints of S/G2, G2/M and mitosis exit, and influences the transcription of two ras genes Ppras1 and Pprap1, as well as the Ras protein level. Antibody neutralization experiment using anti-Ras antibody treatment showed that Ras protein played an important role in cell cycle checkpoint control through regulation of the level of Cyclin B1, suggesting that Ras protein might be a key factor for histone acetylation-mediated cell cycle regulation in P. polycephalum.

  11. Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities

    OpenAIRE

    Benedito Barraviera; Paulo Câmara Marques Pereira; Jussara Marcondes Machado; Maria Julia de Souza; Carlos Roberto G. Lima; Paulo Roberto Curi; Rinaldo Poncio Mendes; Domingos Alves Meira

    1991-01-01

    The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females) aged 17 to 58 years. Twenty one (53.84%) of the patients presented a slow acetylatingphenotype and 18(46.16%) a fast acetylating phenotype. Glucose-6-phosphate- dehydrogenase (G6PD) acti vity was decreased in 5(23.80%) slow acetylator...

  12. Lysine acetylation is a common post-translational modification of key metabolic pathway enzymes of the anaerobe Porphyromonas gingivalis.

    Science.gov (United States)

    Butler, Catherine A; Veith, Paul D; Nieto, Matthew F; Dashper, Stuart G; Reynolds, Eric C

    2015-10-14

    Porphyromonas gingivalis is a Gram-negative anaerobe considered to be a keystone pathogen in the development of the bacterial-associated inflammatory oral disease chronic periodontitis. Although post-translational modifications (PTMs) of proteins are commonly found to modify protein function in eukaryotes and prokaryotes, PTMs such as lysine acetylation have not been examined in P. gingivalis. Lysine acetylation is the addition of an acetyl group to a lysine which removes this amino acid's positive charge and can induce changes in a protein's secondary structure and reactivity. A proteomics based approach combining immune-affinity enrichment with high sensitivity Orbitrap mass spectrometry identified 130 lysine acetylated peptides from 92 P. gingivalis proteins. The majority of these peptides (71) were attributed to 45 proteins with predicted metabolic activity; these proteins could be mapped to several P. gingivalis metabolic pathways where enzymes catalysing sequential reactions within the same pathway were often found acetylated. In particular, the catabolic pathways of complex anaerobic fermentation of amino acids to produce energy had 12 enzymes lysine acetylated. The results suggest that lysine acetylation may be an important mechanism in metabolic regulation in P. gingivalis, which is vital for P. gingivalis survival and adaptation of its metabolism throughout infection. Statement of significance. Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. The ability of the pathogen to induce dysbiosis and disease is related to an array of specific virulence factors and metabolic regulation that enables the bacterium to proliferate in an inflamed periodontal pocket. The mechanisms P. gingivalis uses to adapt to a changing and hostile environment are poorly understood and here we show, for the first time, that enzymes of critical metabolic pathways for energy

  13. Influence of different degrees of acetylation in the physical and mechanical properties of particleboards and wood-cement composites

    Directory of Open Access Journals (Sweden)

    Setsuo Iwakiri

    2014-12-01

    Full Text Available Chemical modified wood particles used to particleboards manufacture may, at the same time, improve the dimensional stability and damage the internal bond. The aim of this research was find the optimal point of acetylation for particleboards. Pinus taeda particles with different degrees of acetylation, 8, 15 and 20% of weight percentage gain (WGP, were used in the production of particleboards with urea-formaldehyde resin and wood-cement composites produced by mechanical and vibratory compaction. It was evaluated the water absorption, thickness swelling and internal bind of the particleboards according to the European standards EN 317 and EN 319. Particleboards produced with 15 WPG showed the lowest water absorption and thickness swelling values. However, the use of chemically modified wood had a negative influence in the internal bind of the boards. This phenomenon can be explain due to the similar behavior between resin and water, that way, the high degree acetylation stops the adhesive and adherent bind. In the case of wood-cement composites, the internal bind improves as the acetylation degrees get higher. Nevertheless the inhibition of acetylated wood particles to the cement hydration got higher when the WPG was higher than 8%.

  14. Histone acetylation influences the transcriptional activation of POX in Beta vulgaris L. and Beta maritima L. under salt stress.

    Science.gov (United States)

    Yolcu, Seher; Ozdemir, Filiz; Güler, Aybüke; Bor, Melike

    2016-03-01

    Acetylation of histone proteins is a type of chromatin modification which facilitates the activation of genes. Recent studies brought up the importance of this reversible and rapid process for the regulation of gene expression especially in plant defense against a variety of environmental stresses. Deciphering the exact mechanisms of chromatin modifications under abiotic stress conditions is important for improving crop plants' performance and yield. In a previous study we compared the salt stress responses of Beta vulgaris (sugar beet) and Beta maritima (wild beet). In accordance with those results we suggested that chromatin remodeling can be an active process in the regulation of genes related to salt stress tolerance of these plants. Therefore we performed ChIP assay in control and salt stressed (250 and 500 mM NaCl) plants and compared the enrichment of acetylation in the associated chromatin sites. We found that the transcriptional activation of one peroxidase (POX) encoding gene was associated with the elevated levels of acetylation in H3K9 and H3K27 sites. The acetylation patterns were remarkably different between two species in which the highest acetylation levels were found at H3K9 and H3K27 in wild beet and sugar beet respectively.

  15. Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation.

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-02-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.

  16. Histone acetylation influences the transcriptional activation of POX in Beta vulgaris L. and Beta maritima L. under salt stress.

    Science.gov (United States)

    Yolcu, Seher; Ozdemir, Filiz; Güler, Aybüke; Bor, Melike

    2016-03-01

    Acetylation of histone proteins is a type of chromatin modification which facilitates the activation of genes. Recent studies brought up the importance of this reversible and rapid process for the regulation of gene expression especially in plant defense against a variety of environmental stresses. Deciphering the exact mechanisms of chromatin modifications under abiotic stress conditions is important for improving crop plants' performance and yield. In a previous study we compared the salt stress responses of Beta vulgaris (sugar beet) and Beta maritima (wild beet). In accordance with those results we suggested that chromatin remodeling can be an active process in the regulation of genes related to salt stress tolerance of these plants. Therefore we performed ChIP assay in control and salt stressed (250 and 500 mM NaCl) plants and compared the enrichment of acetylation in the associated chromatin sites. We found that the transcriptional activation of one peroxidase (POX) encoding gene was associated with the elevated levels of acetylation in H3K9 and H3K27 sites. The acetylation patterns were remarkably different between two species in which the highest acetylation levels were found at H3K9 and H3K27 in wild beet and sugar beet respectively. PMID:26773543

  17. [3H]Indole-3-acetyl-myo-inositol hydrolysis by extracts of Zea mays L. vegetative tissue

    Science.gov (United States)

    Hall, P. J.; Bandurski, R. S.

    1986-01-01

    [3H]Indole-3-acetyl-myo-inositol was hydrolyzed by buffered extracts of acetone powders prepared from 4 day shoots of dark grown Zea mays L. seedlings. The hydrolytic activity was proportional to the amount of extract added and was linear for up to 6 hours at 37 degrees C. Boiled or alcohol denatured extracts were inactive. Analysis of reaction mixtures by high performance liquid chromatography demonstrated that not all isomers of indole-3-acetyl-myo-inositol were hydrolyzed at the same rate. Buffered extracts of acetone powders were prepared from coleoptiles and mesocotyls. The rates of hydrolysis observed with coleoptile extracts were greater than those observed with mesocotyl extracts. Active extracts also catalyzed the hydrolysis of esterase substrates such as alpha-naphthyl acetate and the methyl esters of indoleacetic acid and naphthyleneacetic acid. Attempts to purify the indole-3-acetyl-myo-inositol hydrolyzing activity by chromatographic procedures resulted in only slight purification with large losses of activity. Chromatography over hydroxylapatite allowed separation of two enzymically active fractions, one of which catalyzed the hydrolysis of both indole-3-acetyl-myo-inositol and esterase substrates. With the other enzymic hydrolysis of esterase substrates was readily demonstrated, but no hydrolysis of indole-3-acetyl-myo-inositol was ever detected.

  18. Thiosemicarbazone modification of 3-acetyl coumarin inhibits Aβ peptide aggregation and protect against Aβ-induced cytotoxicity.

    Science.gov (United States)

    Ranade, Dnyanesh S; Bapat, Archika M; Ramteke, Shefali N; Joshi, Bimba N; Roussel, Pascal; Tomas, Alain; Deschamps, Patrick; Kulkarni, Prasad P

    2016-10-01

    Aggregation of amyloid β peptide (Aβ) is an important event in the progression of Alzheimer's disease. Therefore, among the available therapeutic approaches to fight with disease, inhibition of Aβ aggregation is widely studied and one of the promising approach for the development of treatments for Alzheimer's disease. Thiosemicarbazone compounds are known for their variety of biological activities. However, the potential of thiosemicarbazone compounds towards inhibition of Aβ peptide aggregation and the subsequent toxicity is little explored. Herein, we report synthesis and x-ray crystal structure of novel compound 3-acetyl coumarin thiosemicarbazone and its efficacy toward inhibition of Aβ(1-42) peptide aggregation. Our results indicate that 3-acetyl coumarin thiosemicarbazone inhibits Aβ(1-42) peptide aggregation up to 80% compared to the parent 3-acetyl coumarin which inhibits 52%. Further, 3-acetyl coumarin thiosemicarbazone provides neuroprotection against Aβ-induced cytotoxicity in SH-SY5Y cell line. These findings indicate that thiosemicarbazone modification renders 3-acetyl coumarin neuroprotective properties.

  19. [3H]Indole-3-acetyl-myo-inositol hydrolysis by extracts of Zea mays L. vegetative tissue

    International Nuclear Information System (INIS)

    [3H]Indole-3-acetyl-myo-inositol was hydrolyzed by buffered extracts of acetone powders prepared from 4 day shoots of dark grown Zea mays L. seedlings. The hydrolytic activity was proportional to the amount of extract added and was linear for up to 6 hours at 370C. Boiled or alcohol denatured extracts were inactive. Analysis of reaction mixtures by high performance liquid chromatography demonstrated that not all isomers of indole-3-acetyl-myo-inositol were hydrolyzed at the same rate. Buffered extracts of acetone powders were prepared from coleoptiles and mesocotyls. The rates of hydrolysis observed with coleoptile extracts were greater than those observed with mesocotyl extracts. Active extracts also catalyzed the hydrolysis of esterase substrates such as α-naphthyl acetate and the methyl esters of indoleacetic acid and naphthyleneacetic acid. Attempts to purify the indole-3-acetyl-myo-inositol hydrolyzing activity by chromatographic procedures resulted in only slight purification with large losses of activity. Chromatography over hydroxylapatite allowed separation of two enzymically active fractions, one of which catalyzed the hydrolysis of both indole-3-acetyl-myo-inositol and esterase substrates. With the other fraction enzymic hydrolysis of esterase substrates was readily demonstrated, but no hydrolysis of indole-3-acetyl-myo-inositol was ever detected

  20. Acetylation of alcohols and phenols under solvent-free conditions using copper zirconium phosphate

    Institute of Scientific and Technical Information of China (English)

    Abdol R. Hajipour; Hirbod Karimi

    2014-01-01

    Copper zirconium phosphate nanoparticles have been used as an efficient catalyst for the acetyla‐tion of a wide range of alcohols and phenols with acetic anhydride in good to excellent yields under solvent‐free conditions. The steric and electronic properties of the different substrates had a signif‐icant influence on the reaction conditions required to achieve the acetylation. The catalyst used in the current study was characterized by inductively‐coupled plasma optical emission spectroscopy, energy dispersive spectroscopy, X‐ray diffraction, N2 adsorption‐desorption, scanning electron microscopy, and transmission electron microscopy. These analyses revealed that the interlayer distance in the catalyst increased from 7.5 to 8.0 Å when Cu2+was intercalated between the layers, whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered and reused at least six times without any discernible decrease in its catalytic activity. This new method for the acetylation of alcohols and phenols has several key advantages, including mild and environmentally friendly reaction conditions, as well as good to excellent yields and a facile work‐up.

  1. Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response.

    Science.gov (United States)

    Ghari, Fatemeh; Quirke, Anne-Marie; Munro, Shonagh; Kawalkowska, Joanna; Picaud, Sarah; McGouran, Joanna; Subramanian, Venkataraman; Muth, Aaron; Williams, Richard; Kessler, Benedikt; Thompson, Paul R; Fillipakopoulos, Panagis; Knapp, Stefan; Venables, Patrick J; La Thangue, Nicholas B

    2016-02-01

    Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression. PMID:26989780

  2. Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency.

    Science.gov (United States)

    Saunier, Chloé; Støve, Svein Isungset; Popp, Bernt; Gérard, Bénédicte; Blenski, Marina; AhMew, Nicholas; de Bie, Charlotte; Goldenberg, Paula; Isidor, Bertrand; Keren, Boris; Leheup, Bruno; Lampert, Laetitia; Mignot, Cyril; Tezcan, Kamer; Mancini, Grazia M S; Nava, Caroline; Wasserstein, Melissa; Bruel, Ange-Line; Thevenon, Julien; Masurel, Alice; Duffourd, Yannis; Kuentz, Paul; Huet, Frédéric; Rivière, Jean-Baptiste; van Slegtenhorst, Marjon; Faivre, Laurence; Piton, Amélie; Reis, André; Arnesen, Thomas; Thauvin-Robinet, Christel; Zweier, Christiane

    2016-08-01

    N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype-phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females. PMID:27094817

  3. [Separation and properties of N-acetyl-beta-D-glucosaminidase from human seminal plasma].

    Science.gov (United States)

    Yoshida, K; Uchijima, Y; Kobayashi, N; Saitoh, H

    1989-11-01

    N-acetyl-beta-D-glucosaminidase from human seminal plasma has been separated by the cellulose acetate electrophoresis into two components, isoenzyme I and II. The two isoenzymes are readily separated on a DEAE-Sephadex column. Isoenzyme I which has adsorbed to the column, is eluted at 0.1 M NaCl, whereas isoenzyme II has passed through the column. The following enzyme properties have been obtained: 1) Both isoenzymes show the same Km values (0.27 X 10(-3) M) towards sodio-m-cresol-sufonphtaleinyl-N-acetyl-beta-D-glucosaminide . 2) Both isoenzymes show the same pH optima of 5.4. 3) Optimal temperature for isoenzyme I is 50 degrees C, while that for isoenzyme II is 65 degrees C. Isoenzyme II is heat stable, while isoenzyme I is easily denatured by heat. These characteristics of isoenzyme I and II coincide with previous reports of NAG A and B from the spleen and the kidney, respectively. The activity ratio of isoenzyme I and II has been studied for the reproductive tissues. The % ratio of isoenzyme I and II in the epididymal head is 62 and 38, that in the epididymal tail is 42 and 58, and 38:62 in the seminal vesicle, 35:65 in the prostatic gland and 27:73 in the seminal plasma. PMID:2593437

  4. Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity.

    Directory of Open Access Journals (Sweden)

    Minghao He

    Full Text Available The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.

  5. Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function.

    Science.gov (United States)

    Messner, Simon; Schuermann, David; Altmeyer, Matthias; Kassner, Ingrid; Schmidt, Darja; Schär, Primo; Müller, Stefan; Hottiger, Michael O

    2009-11-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated nuclear protein and functions as a molecular stress sensor. At the cellular level, PARP1 has been implicated in a wide range of processes, such as maintenance of genome stability, cell death, and transcription. PARP1 functions as a transcriptional coactivator of nuclear factor kappaB (NF-kappaB) and hypoxia inducible factor 1 (HIF1). In proteomic studies, PARP1 was found to be modified by small ubiquitin-like modifiers (SUMOs). Here, we characterize PARP1 as a substrate for modification by SUMO1 and SUMO3, both in vitro and in vivo. PARP1 is sumoylated at the single lysine residue K486 within its automodification domain. Interestingly, modification of PARP1 with SUMO does not affect its ADP-ribosylation activity but completely abrogates p300-mediated acetylation of PARP1, revealing an intriguing crosstalk of sumoylation and acetylation on PARP1. Genetic complementation of PARP1-depleted cells with wild-type and sumoylation-deficient PARP1 revealed that SUMO modification of PARP1 restrains its transcriptional coactivator function and subsequently reduces gene expression of distinct PARP1-regulated target genes.

  6. Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades.

    Science.gov (United States)

    Bahrami, Yadollah; Franco, Christopher M M

    2016-01-01

    Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ(7(8)) or Δ(9(11)) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. PMID:27527190

  7. Flavonoids with acetylated branched glycans and bioactivity of Tipuana tipu (Benth.) Kuntze leaf extract.

    Science.gov (United States)

    Afifi, Manal S; Elgindi, Omaima D; Bakr, Reham O

    2014-01-01

    The new acetylated kaempferol tetraglycoside, kaempferol-3-O-[2″(4-acetylrhamnopyranosyl)-3″-galactopyranosyl] robinobioside (1), was isolated from the aqueous methanolic leaf extract of Tipuana tipu Benth. The known kaempferol 3-[2″-(4-acetyl-rhamnosyl)] robinobioside (2), kaempferol 3-O-2″-rhamnopyranosylrutinoside (3), rutin (4), kaempferol 3-O-rutinoside (5), kaempferol 3-O-glucopyranoside (6), kaempferol 3-O-galactopyranoside (7), quarcetin 3-O-glucopyranoside (8), kaempferol (9) and quercetin (10) together with the chlorogenic acid (11) were also isolated and characterised. Structures were established on the basis of chemical and spectroscopic analysis including (1)H NMR, (13)C NMR, 2D NMR and ESI-MS. The methanol extract exhibited moderate antioxidant activity, IC50 28.96 μg/mL, compared with ascorbic acid (1.83 μg/mL) and tertiary-butylhydroquinone (1.92 μg/mL). The methanol and chloroform extracts exhibited potent cytotoxic activity; the former was found to be active against larynx and liver cell lines, while the latter being active against intestine and liver cell lines.

  8. NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Qi; Zheng, Xingzheng; McNutt, Michael A.; Guang, Lizhao; Sun, Ying; Wang, Jiaochen; Gong, Yilei; Hou, Lin [Department of Pathology, Health Science Center of Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Zhang, Bo, E-mail: zhangbo@bjmu.edu.cn [Department of Pathology, Health Science Center of Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China)

    2009-06-10

    The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase. The domain in N-terminal residues 549-834 of NAT10 specifically mediated its subcellular localization. Treatment with genotoxic agents or irradiation increased concentration of NAT10 in both the nucleolus and midbody. Moreover, DNA damage induced increase of NAT10 in the midbody apparently accompanied by in situ elevation of the level of acetylated {alpha}-tubulin, suggesting that it plays a role in maintaining or enhancing stability of {alpha}-tubulin. The depletion of NAT10 induced defects in nucleolar assembly, cytokinesis and decreased acetylated {alpha}-tubulin, leading to G2/M cell cycle arrest or delay of mitotic exit. In addition, over-expression of NAT10 was found in a variety of soft tissue sarcomas, and correlated with tumor histological grading. These results indicate that NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules.

  9. Effects of MAPP Compatibilization and Acetylation Treatment Followed by Hydrothermal Aging on Polypropylene Alfa Fiber Composites

    Directory of Open Access Journals (Sweden)

    Noura Hamour

    2015-01-01

    Full Text Available This work investigates the effect of hydrothermal aging on the properties of polypropylene/alfa fiber composites. Hydrothermal aging was induced in an environmental testing chamber at 65°C and 75% relative humidity (RH over a 1000 h period. At the beginning (t=0 h, the results showed that Young’s moduli of the untreated alfa fibers and the acetylation-treated fibers increased by 21% and 36%, respectively, compared with the virgin polypropylene (PP. Additionally, Young’s moduli decreased by 7% for the compatibilized composites composed of maleic anhydride grafted polypropylene (MAPP. After 1000 h of aging, Young’s moduli decreased by 36% for untreated alfa fibers and 29% for the acetylation-treated alfa fibers and the compatibilized composites. Significant degradation was observed in the untreated alfa fiber samples. The Fourier transformed infrared (FTIR allows us to distinguish the characteristic absorption bands of the main chemical functions present in the composite material before and after aging. The thermal properties showed that the thermal stability and the degree of crystallinity of the composites decreased after hydrothermal aging; this result was corroborated by the dynamical mechanical analysis (DMA results.

  10. An efficient acetylation of dextran using in situ activated acetic anhydride with iodine

    Directory of Open Access Journals (Sweden)

    MUHAMMAD A. HUSSAIN

    2010-02-01

    Full Text Available A facile, efficient, cost-effective and solvent-free acetylation method has been developed for the acetylation of dextran. Dextran acetates were successfully synthesized using different molar ratios of acetic anhydride in the presence of iodine as a catalyst without the use of any solvent. The reactions were realized at 50 °C for 3 h under stirring and nitrogen. This efficient method yielded highly pure and organosoluble dextran esters. The reaction appears highly effective for obtaining higher degrees of substitution (DS with great efficiency. Under solvent-free conditions, dextran triacetates were efficiently synthesized. It was also observed that the molar ratio can easily control the DS of pendant groups onto the polymer backbone. Hence, a range of products with varying DS were successfully designed, purified and characterized. Covalent attachment of the pendant groups onto the polymer backbone was verified by spectroscopic techniques. Thermogravimetric analysis indicated that the obtained dextran esters were thermally as stable as dextran. The DS of the pendant groups onto the polymer backbone was calculated using standard acid base titration after saponification. Furthermore, all products were thoroughly characterized by thermal analysis (TG and DTG, and FTIR and 1H-NMR spectroscopic analysis.

  11. Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

    Science.gov (United States)

    Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W

    2016-01-01

    Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. PMID:26441064

  12. N-acetyl-l-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates

    Science.gov (United States)

    Baslow, Morris H.; Guilfoyle, David N.

    2015-01-01

    N-acetyl-l-histidine (NAH) is a prominent biomolecule in brain, retina and lens of poikilothermic vertebrates. In fish lens, NAH exhibits an unusual compartmentalized metabolism. It is synthesized from l-histidine (His) and acetyl Co-enzyme A. However, NAH cannot be catabolized by lens cells. For its hydrolysis, NAH is exported to ocular fluid where a specific acylase cleaves His which is then actively taken up by lens and re-synthesized into NAH. This energy-dependent cycling suggested a pump mechanism operating at the lens/ocular fluid interface. Additional studies led to the hypothesis that NAH functioned as a molecular water pump (MWP) to maintain a highly dehydrated lens and avoid cataract formation. In this process, each NAH molecule released to ocular fluid down its gradient carries with it 33 molecules of bound water, effectively transporting the water against a water gradient. In ocular fluid the bound water is released for removal from the eye by the action of NAH acylase. In this paper, we demonstrate for the first time the identification of NAH in fish brain using proton magnetic resonance spectroscopy (MRS) and describe recent evidence supporting the NAH MWP hypothesis. Using MRS, we also document a phylogenetic transition in brain metabolism between poikilothermic and homeothermic vertebrates. PMID:25919898

  13. Cloning and characterization of cotton heteromeric acetyl-CoA carboxylase genes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Heteromeric acetyl-coanzyme A(CoA)carboxylese(ACCase)catalyzes the formation of malonyl-CoA from acetyl-CoA.It plays an essential role in fatty acid synthesis in prokaryotes and most of plants.The heteromeric ACCase is composed of four subunits:biotin carboxylase (BC),biotin carboxyl carrier protein (BCCP),and α-and β-subunits of carboxyltransferese(α-andβ-CT).In this study,we cloned five novel genes encoding the subunits of heteromeric ACCese(one BC,BCCP and β-CT,and two α-CTs) from cotton (Gossypium hirsutum cv.zhongmian 35)by RACE-PCR.The deduced amino acid sequence of these cDNAs shares high similarity with other reported heteromeric ACCese subunits.The phylogenetic analysis indicated that the different subunits of heteromeric ACCase were grouped in a similar pattern.Southern blot analysis revealed the milti-copy patterns of these heteromeric ACCase genes in cotton genome.Semi-quantitative RT-PCR demonstrated that heteromeric ACCese genes were constitutively expressed in all of the cotton tissues,but the transcripts accumulated at a relatively low level in roots.To our knowledge,this is the first report about characterization of the heteromeric ACCase genes in cotton.

  14. Ecotoxicity evaluation and removal of sulfonamides and their acetylated metabolites during conventional wastewater treatment.

    Science.gov (United States)

    García-Galán, María Jesús; González Blanco, Susana; López Roldán, Ramón; Díaz-Cruz, Silvia; Barceló, Damiá

    2012-10-15

    The present study describes the evaluation of the risk posed by the occurrence of sulfonamides (SAs) in wastewaters. A fully automated analytical method based on on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (on line SPE-LC-MS/MS) was developed, validated and applied for the analysis of sixteen SAs and, for the first time in wastewaters and sewage sludge, five of their acetylated metabolites. Influent and effluent samples from twenty two different wastewater treatment plants (WWTPs) in Catalonia (Spain) and sewage sludge from fifteen of them were analyzed; removal rates (RE%) and half-lives (t(1/2)) for each SA were calculated. The estimated correlations between RE% and to the hydraulic retention time (HRT) of the different plants indicated no clear influence of HRT on removals. Sulfamethoxazole (SMX), sulfapyridine (SPY) and their corresponding acetylated metabolites were detected with the highest frequencies of detection and at the highest concentrations. The ecotoxicity of both SPY and AcSPY was evaluated for the first time through bioluminescent inhibition assays, resulting in a higher toxicity being attributed to the metabolite. Finally, the potential environmental risk posed by the levels of SAs detected was evaluated calculating the hazard quotients (HQ) to different non-target aquatic organisms in treated wastewaters. SMX was the only SA posing a risk to algae, with an HQ>10. PMID:22960452

  15. Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades

    Science.gov (United States)

    Bahrami, Yadollah; Franco, Christopher M. M.

    2016-01-01

    Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ7(8) or Δ9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. PMID:27527190

  16. Entamoeba histolytica acetyl-CoA synthetase:biomarker of acute amoebic liver abscess

    Institute of Scientific and Technical Information of China (English)

    Lim Boon Huat; Pim Chau Dam; Alfonso Olivos Garcia; Tan Zi Ning; Wong Weng Kin; Rahmah Noordin; Siti Shafiqah Anaqi Azham; Lee Zhi Jie; Guee Cher Ching; Foo Phiaw Chong

    2014-01-01

    Objective: To characterize the Entamoeba histolytica (E. histolytica) antigen(s) recognized by moribound amoebic liver abscess hamsters.Methods:in 1D- and 2D-Western blot analyses. The antigenic protein was then sent for tandem mass spectrometry analysis. The corresponding gene was cloned and expressed in Escherichia coli BL21-AI to produce the recombinant E. histolytica ADP-forming acetyl-CoA synthetase (EhACS) protein. A customised ELISA was developed to evaluate the sensitivity and specificity of the recombinant protein.Results:Crude soluble antigen of E. histolytica was probed with sera of moribund hamsters detected by sera of hamsters in the control group. Tandem mass spectrometry analysis revealed the protein to be the 77 kDa E. histolytica ADP-forming acetyl-CoA synthetase (EhACS). The customised ELISA results revealed 100% sensitivity and 100% specificity when tested against infected (n=31) and control group hamsters (n=5) serum samples, respectively.Conclusions:This finding suggested the significant role of EhACS as a biomarker for moribund A ~75 kDa protein band with a pI value of 5.91-6.5 was found to be antigenic; and not hamsters with acute amoebic liver abscess (ALA) infection. It is deemed pertinent that future studies explore the potential roles of EhACS in better understanding the pathogenesis of ALA; and in the development of vaccine and diagnostic tests to control ALA in human populations.

  17. N-acetyl-l-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates

    Directory of Open Access Journals (Sweden)

    Morris H. Baslow

    2015-04-01

    Full Text Available N-acetyl-l-histidine (NAH is a prominent biomolecule in brain, retina and lens of poikilothermic vertebrates. In fish lens, NAH exhibits an unusual compartmentalized metabolism. It is synthesized from L-histidine (His and acetyl Co-enzyme A. However, NAH cannot be catabolized by lens cells. For its hydrolysis, NAH is exported to ocular fluid where a specific acylase cleaves His which is then actively taken up by lens and re-synthesized into NAH. This energy-dependent cycling suggested a pump mechanism operating at the lens/ocular fluid interface. Additional studies led to the hypothesis that NAH functioned as a molecular water pump (MWP to maintain a highly dehydrated lens and avoid cataract formation. In this process, each NAH molecule released to ocular fluid down its gradient carries with it 33 molecules of bound water, effectively transporting the water against a water gradient. In ocular fluid the bound water is released for removal from the eye by the action of NAH acylase. In this paper, we demonstrate for the first time the identification of NAH in fish brain using proton magnetic resonance spectroscopy (MRS and describe recent evidence supporting the NAH MWP hypothesis. Using MRS, we also document a phylogenetic transition in brain metabolism between poikilothermic and homeothermic vertebrates.

  18. Chitinase but N-acetyl-β-D-glucosaminidase production correlates to the biomass decline in Penicillium and Aspergillus species.

    Science.gov (United States)

    Pusztahelyi, Tünde; Pócsi, István

    2014-06-01

    Hydrolytic enzyme production is typical of the autolysis in filamentous fungi; however, less attention has been given to the physiological role of the enzymes. Here, the aim was to investigate the possible relation of the chitinolytic enzymes to the changes in the biomass in some filamentous fungi of high importance for pharmaceutical or food industry. In Penicillium and Aspergillus filamentous fungi, which showed different characteristics in submerged cultures, the growth and biomass decline rates were calculated and correlated to the chitinase and N-acetyl-β-D-glucosaminidase enzyme productions. Correlation was found between the biomass decrease rate and the chitinase level at the stationary growth phase; while chitinase production covariates negatively with N-acetyl-β-D-glucosaminidase activities. The chitinase production and the intensive autolysis hindered the production of N-acetyl-β-D-glucosaminidase and, therefore, could hinder the cell death in the cultures.

  19. Metalloproteins/metalloenzymes for the synthesis of acetyl-CoA in the Wood-Ljungdahl pathway

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This paper focuses on the group of metalloproteins/metalloenzymes in the acetyl-coenzyme A synthesis pathway of anaerobic microbes called Wood-Ljungdahl pathway,including formate dehydrogenase (FDH),corrinoid iron sulfur protein (CoFeSP),acetyl-CoA synthase (ACS) and CO dehydrogenase (CODH). FDH,a key metalloenzyme involved in the conversion of carbon dioxide to methyltetrahydrofolate,catalyzes the reversible oxidation of formate to carbon dioxide. CoFeSP,as a methyl group transformer,accepts the methyl group from CH3-H4 folate and then transfers it to ACS. CODH reversibly catalyzes the reduction of CO2 to CO and ACS functions for acetyl-coenzyme A synthesis through condensation of the methyl group,CO and coenzyme A,to finish the whole pathway. This paper introduces the structure,function and reaction mechanisms of these enzymes.

  20. Antimycobacterial activity of two natural alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian shrub Adhatoda vasica Ness. leaves

    Indian Academy of Sciences (India)

    S Ignacimuthu; N Shanmugam

    2010-12-01

    In folk medicine, Adhatoda vasica Ness. (Acanthaceae) is used to treat asthma and cough. The leaves of A.vasica were powdered and extracted with hexane, ethyl acetate and methanol. The hexane extract showed 97% reduction in colony-forming units (CFU) at 100 g/ml. The hexane extract was subjected to column chromatography. Two natural compounds, vasicine acetate and 2-acetyl benzylamine, were isolated from it. They were bioassayed against Mycobacterium tuberculosis. The two compounds showed strong antimycobacterial activity. Vasicine acetate and 2-acetyl benzylamine isolated from hexane extract of A. vasica leaves, significantly inhibited M. tuberculosis and one multi-drug-resistant (MDR) strain and one sensitive strain at 200 and 50 g/ml, respectively. Our study demonstrated that both the compounds, vasicine acetate and 2-acetyl benzylamine, could be evaluated further for developing a drug to control M. tuberculosis.

  1. Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni*

    Science.gov (United States)

    Ha, Reuben; Frirdich, Emilisa; Sychantha, David; Biboy, Jacob; Taveirne, Michael E.; Johnson, Jeremiah G.; DiRita, Victor J.; Vollmer, Waldemar; Clarke, Anthony J.; Gaynor, Erin C.

    2016-01-01

    Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, its mechanisms of pathogenesis are poorly understood. Peptidoglycan (PG) is important for helical shape, colonization, and host-pathogen interactions in C. jejuni. Therefore, changes in PG greatly impact the physiology of this organism. O-acetylation of peptidoglycan (OAP) is a bacterial phenomenon proposed to be important for proper cell growth, characterized by acetylation of the C6 hydroxyl group of N-acetylmuramic acid in the PG glycan backbone. The OAP gene cluster consists of a PG O-acetyltransferase A (patA) for translocation of acetate into the periplasm, a PG O-acetyltransferase B (patB) for O-acetylation, and an O-acetylpeptidoglycan esterase (ape1) for de-O-acetylation. In this study, reduced OAP in ΔpatA and ΔpatB had minimal impact on C. jejuni growth and fitness under the conditions tested. However, accumulation of OAP in Δape1 resulted in marked differences in PG biochemistry, including O-acetylation, anhydromuropeptide levels, and changes not expected to result directly from Ape1 activity. This suggests that OAP may be a form of substrate level regulation in PG biosynthesis. Ape1 acetylesterase activity was confirmed in vitro using p-nitrophenyl acetate and O-acetylated PG as substrates. In addition, Δape1 exhibited defects in pathogenesis-associated phenotypes, including cell shape, motility, biofilm formation, cell surface hydrophobicity, and sodium deoxycholate sensitivity. Δape1 was also impaired for chick colonization and adhesion, invasion, intracellular survival, and induction of IL-8 production in INT407 cells in vitro. The importance of Ape1 in C. jejuni biology makes it a good candidate as an antimicrobial target. PMID:27474744

  2. 蚕丝织物乙酰化抗皱整理%Wrinkle resistant finishing of silk by acetylating

    Institute of Scientific and Technical Information of China (English)

    陈程; 张光先; 邓娜; 张凤秀

    2012-01-01

    This paper studied the wrinkle resistant finishing of silk by partial acetylation. The acetylated silk was characterized by infrared spectrum, X-ray diffraction and DSC. And the wearability was also measured. The results showed that the wrinkle elasticity of the acetylated silk was enhanced by a great margin, with slow and acute crease recovery angles improved from 218.5?to 270.5?and 168.5?to 210.5? respectively. This suggested that the non-crosslinking finishing agent which only decreases the capacity to form hydrogen bonds can also increase the wrinkle elasticity of silk greatly. Infrared spectral analysis showed that the Beta-sheet structure of the acetylated silk increased and amino group partially acetylated. X-ray diffraction analysis showed that the degree of crystallization of the acetylated silk increased. DSC analysis showed that the acetylated silk's decomposition temperature and thermal stability increased. At the same time, the moisture regain, whiteness and breaking strength of the acetylated silk exhibited little change, with flexural stiffness improved a little.%研究了蚕丝织物部分乙酰化的抗皱整理,同时对乙酰化蚕丝织物进行了红外光谱、X-射线衍射、DSC以及服用性能测试分析.结果显示,乙酰化蚕丝织物折皱弹性大幅提高,缓弹和急弹折皱回复角分别由218.5°和168.5°提升到270.5°和210.5°,结果表明,只降低蚕丝织物形成氢键能力的非交联型整理剂也能大幅度提高蚕丝织物的折皱弹性 ;红外光谱分析表明,乙酰化蚕丝织物的β折叠结构增加,氨基被部分乙酰化 ;X-射线衍射分析表明乙酰化蚕丝织物的结晶度增加 ;DSC分析表明,乙酰化蚕丝织物的分解温度提高,热稳定性增加 ;乙酰化蚕丝织物的回潮率、白度、断裂强力等基本无变化,其刚柔度有所增加,挺括性提高.

  3. P0525 : N-Acetylated alpha smooth muscle actin levels are increased in hepatic fibrosis but decreased in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Nielsen, M.J.; Nielsen, Signe Holm; Hansen, N.U.B.;

    2015-01-01

    Alpha Smooth Muscle Actin (a-SMA) is upregulated together with extracellular matrix (ECM) during activation of Hepatic Stellate Cells (HSCs) in fibrosis. Histone deacetylase (HDAC) remove acetylations and regulate the expression of genes, which is associated with cancers. There is a close...... relationship between cirrhosis and hepatocellular carcinoma (HCC), and markers enabling identification of patients in risk of developing HCC with cirrhosis is a major unmet clinical need. We developed an ELISA for the assessment of acetylated a-SMA (Aca- SMA) in serum. The objective was to investigate...

  4. RASSF1A Suppresses Cell Migration through Inactivation of HDAC6 and Increase of Acetylated α-Tubulin

    OpenAIRE

    Jung, Hae-Yun; Jung, Jun Seok; Whang, Young Mi; Kim, Yeul Hong

    2013-01-01

    Purpose The RAS association domain family protein 1 (RASSF1) has been implicated in a tumor-suppressive function through the induction of acetylated α-tubulin and modulation of cell migration. However, the mechanisms of how RASSF1A is associated with acetylation of α-tubulin for controlling cell migration have not yet been elucidated. In this study, we found that RASSF1A regulated cell migration through the regulation of histon deacetylase 6 (HDAC6), which functions as a tubulin deacetylase. ...

  5. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB

    OpenAIRE

    Chen, Lin-Feng; Mu, Yajun; Greene, Warner C.

    2002-01-01

    The nuclear function of the heterodimeric NF-κB transcription factor is regulated in part through reversible acetylation of its RelA subunit. We now demonstrate that the p300 and CBP acetyltransferases play a major role in the in vivo acetylation of RelA, principally targeting lysines 218, 221 and 310 for modification. Analysis of the functional properties of hypoacetylated RelA mutants containing lysine-to-arginine substitutions at these sites and of wild-type RelA co-expressed in the presen...

  6. Topical effects of N-acetyl-L-hydroxyproline on ceramide synthesis and alleviation of pruritus

    Directory of Open Access Journals (Sweden)

    Hashizume E

    2013-02-01

    Full Text Available Erika Hashizume,1 Tetsuo Nakano,2 Ayako Kamimura,1 Koji Morishita31Healthcare Products Development Center, Kyowa Hakko Bio, Tsukuba, Ibaraki, 2Technical Research Laboratories, Kyowa Hakko Bio, Hofu, Yamaguchi, 3Technology Development and Research Department, Kyowa Hakko Bio, Tokyo, JapanPurpose: N-acetyl-l-hydroxyproline (AHYP is an acetylated form of l-hydroxyproline that is used to treat skin ulcers and porphyria cutanea tarda. Its other biological and physiological effects on the skin have not been elucidated. We investigated the effects of AHYP on the skin-barrier function, focusing on ceramide synthesis and the effects of topical AHYP on atopic dermatitis.Materials and methods: AHYP was applied to a three-dimensional cultured skin model. Ceramides were quantified by high-performance thin-layer chromatography. Serine palmitoyltransferase (SPT is the rate-limiting enzyme in de novo ceramide synthesis, and the mRNA of its long-chain base subunit 1 (SPTLC1 was evaluated by quantitative reverse-transcription polymerase chain reaction. A clinical trial in the form of an intraindividual, comparative, double-blind, randomized, vehicle-controlled test involving 15 female subjects suffering from slight atopic dermatitis was performed. Subjects applied 1% (w/w AHYP cream to one forearm and a control cream to the other forearm twice daily for 4 weeks. Skin condition was evaluated by measuring transepidermal water loss (TEWL. Dermatological observations were made by a dermatologist, and subjects evaluated their own pruritus intensity before beginning treatment and 4 weeks after the start of treatment.Results: SPTLC1 expression and ceramide synthesis were significantly increased in an AHYP-treated skin model (P < 0.05. In the clinical trial, no adverse effects were observed in any subjects. TEWL was increased in the control-treated region of the forearm (P < 0.05 after 4 weeks' application, whereas there was no change in the AHYP-treated region of the

  7. Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: Pathway stoichiometry, free-energy conservation and redox-cofactor balancing

    NARCIS (Netherlands)

    Van Rossum, H.M.; Kozak, B.U.; Pronk, J.T.; Van Maris, A.J.A.

    2016-01-01

    Saccharomyces cerevisiae is an important industrial cell factory and an attractive experimental model for evaluating novel metabolic engineering strategies. Many current and potential products of this yeast require acetyl coenzyme A (acetyl-CoA) as a precursor and pathways towards these products are

  8. Intra- and inter-nucleosomal interactions of the histone H4 tail revealed with a human nucleosome core particle with genetically-incorporated H4 tetra-acetylation.

    Science.gov (United States)

    Wakamori, Masatoshi; Fujii, Yoshifumi; Suka, Noriyuki; Shirouzu, Mikako; Sakamoto, Kensaku; Umehara, Takashi; Yokoyama, Shigeyuki

    2015-11-26

    Post-translational modifications (PTMs) of histones, such as lysine acetylation of the N-terminal tails, play crucial roles in controlling gene expression. Due to the difficulty in reconstituting site-specifically acetylated nucleosomes with crystallization quality, structural analyses of histone acetylation are currently performed using synthesized tail peptides. Through engineering of the genetic code, translation termination, and cell-free protein synthesis, we reconstituted human H4-mono- to tetra-acetylated nucleosome core particles (NCPs), and solved the crystal structures of the H4-K5/K8/K12/K16-tetra-acetylated NCP and unmodified NCP at 2.4 Å and 2.2 Å resolutions, respectively. The structure of the H4-tetra-acetylated NCP resembled that of the unmodified NCP, and the DNA wrapped the histone octamer as precisely as in the unmodified NCP. However, the B-factors were significantly increased for the peripheral DNAs near the N-terminal tail of the intra- or inter-nucleosomal H4. In contrast, the B-factors were negligibly affected by the H4 tetra-acetylation in histone core residues, including those composing the acidic patch, and at H4-R23, which interacts with the acidic patch of the neighboring NCP. The present study revealed that the H4 tetra-acetylation impairs NCP self-association by changing the interactions of the H4 tail with DNA, and is the first demonstration of crystallization quality NCPs reconstituted with genuine PTMs.

  9. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available A major focus of current research into gene induction relates to chromatin and nucleosomal regulation, especially the significance of multiple histone modifications such as phosphorylation, acetylation, and methylation during this process. We have discovered a novel physiological characteristic of all lysine 4 (K4-methylated histone H3 in the mouse nucleus, distinguishing it from lysine 9-methylated H3. K4-methylated histone H3 is subject to continuous dynamic turnover of acetylation, whereas lysine 9-methylated H3 is not. We have previously reported dynamic histone H3 phosphorylation and acetylation as a key characteristic of the inducible proto-oncogenes c-fos and c-jun. We show here that dynamically acetylated histone H3 at these genes is also K4-methylated. Although all three modifications are proven to co-exist on the same nucleosome at these genes, phosphorylation and acetylation appear transiently during gene induction, whereas K4 methylation remains detectable throughout this process. Finally, we address the functional significance of the turnover of histone acetylation on the process of gene induction. We find that inhibition of turnover, despite causing enhanced histone acetylation at these genes, produces immediate inhibition of gene induction. These data show that all K4-methylated histone H3 is subject to the continuous action of HATs and HDACs, and indicates that at c-fos and c-jun, contrary to the predominant model, turnover and not stably enhanced acetylation is relevant for efficient gene induction.

  10. A STUDY OF THE EFFECT OF ACETYLATION ON HEMP FIBRES WITH VINYL ACETATE

    Directory of Open Access Journals (Sweden)

    Nilgül Özmen

    2012-07-01

    Full Text Available Chemical modifications of hemp fibers were performed with acetic anhydride (AA and vinyl acetate (VA in the presence of pyridine or potassium carbonate as catalysts. Hemp fibers (Cannabis sativa were successfully acetylated by VA in the presence of potassium carbonate (15% WPG, but no weight gain was obtained when pyridine was used as catalyst. Hemp fibers were also modified with acetic anhydride (AA in the presence of potassium carbonate and pyridine as catalyst (14% and 16% WPG, respectively under identical conditions, and the results were compared with those obtained using the VA technique. AA-modified, VA-modified, and control hemp fibers were characterized by Infrared (FTIR, 13C CP MAS NMR and thermo gravimetric analysis (TGA.

  11. Characterization of the conglomerate form of acetyl-DL-leucine by thermal analysis and solubility measurements

    Science.gov (United States)

    Estime, N.; Pena, R.; Teychené, S.; Autret, J. M.; Biscans, B.

    2012-03-01

    Starting from a mixture of enantiomers in solution, crystallization can generate different types of crystals. In order to determine which type of crystal is obtained in the case of acetyl leucine, an active pharmaceutical ingredient (API), analytical methods have been used to partially elucidate the binary and ternary phase diagrams of the system composed of the two enantiomers and water. The melting temperature phase diagram of this compound has been obtained by using differential scanning calorimetry (DSC) analyzes. The results show that it is characteristic of a conglomerate. This mode of crystallization has also been confirmed by X-ray powder diffraction analysis. Solubility measurements of enantiomerical mixtures in water enabled the determination of the ternary diagram of solubility. The empiric Meyerhoffer double solubility rule has been modified, due to the characterization of interactions between enantiomers.

  12. Functional properties of acetylated and succinylated cowpea protein concentrate and effect of enzymatic hydrolysis on solubility.

    Science.gov (United States)

    Mune Mune, Martin Alain; Minka, Samuel René; Mbome, Israël Lape

    2011-06-01

    The present study was undertaken to improve functional properties of cowpea protein concentrate by acylation and partial hydrolysis with pepsin. The acylated concentrate showed significant improvement in protein solubility and water solubility index, at neutral pH. In addition, acylation increased fat absorption capacity compared with the untreated concentrate, and the maximum was obtained at 0.75 g succinic anhydride/g concentrate. Acetylation at concentrations of 0.25-0.50 g/g led to the higher emulsifying activity, and a markedly improvement in emulsifying stability was observed at 1.0 g anhydride/g concentrate. Foaming activity increased following acylation, particularly at 0.25 and 1.00 g/g succinic anhydride/g concentrate, while foam stability decreased. At pH 3.5, protein solubility of the acylated concentrates was low ( < 8%). Partial hydrolysis of cowpea protein concentrate with pepsin increased protein solubility at the isoelectric and neutral pH.

  13. FT-Raman and FTIR-ATR spectroscopies and DFT calculations of triterpene acetyl aleuritolic acid

    Science.gov (United States)

    Melo, I. R. S.; Teixeira, A. M. R.; Sena Junior, D. M.; Santos, H. S.; Albuquerque, M. R. J. R.; Bandeira, P. N.; Rodrigues, A. S.; Braz-Filho, R.; Gusmão, G. O. M.; Silva, J. H.; Faria, J. L. B.; Bento, R. R. F.

    2014-01-01

    Triterpenoids comprise an important class of compounds presenting a wide range of biologically important properties. Acetyl aleutitolic acid (AAA) is a triterpenoid isolated from Croton zehntneri, with molecular formula C32H50O4. Its structure has been characterized by NMR spectroscopy, however, there are no papers available regarding its vibrational properties. The Fourier-Transform Infrared with Attenuated Total Reflectance and Fourier-Transform Raman spectra, together with Density Functional Theory calculations of AAA are reported. Vibrational spectra were recorded at 300 K in the regions 600 cm-1 to 4000 cm-1 and 40 cm-1 to 4000 cm-1, for IR and Raman, respectively. Vibrational wavenumbers were predicted using Density Functional Theory calculations with the hybrid functional B3LYP and the basis set 6-31 G(d,p). A complete assignment of vibrational modes is given.

  14. Synthesis of (2-pyridyl)-Acetyl Chitosan and Its Antioxidant Activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Rongchun [Dezhou Univ., Dezhou (China)

    2011-10-15

    In this paper, chloracetyl chitosan (CACTS) was prepared at first. In the molecules of CACTS, there are active chlorine groups, which can take part in other reactions. Thus, number of chitosan derivatives will be obtained after chlorine is substituted. Choosing pyridine as the active group, a novel water-soluble chitosan derivative, (2-pyridyl)-acetyl chitosan (PACTS) was obtained and its antioxidant activity against hydroxyl radicals and superoxide radicals was assessed. The results indicated that PACTS had better antioxidant activity than that of chitosan, carboxymethyl chitosan (CMCTS), hydroxypropyl chitosan (HPCTS), and Vitamin C. And the IC{sub 50} values against hydroxyl radicals and superoxide radicals were 0.31 mg/mL and 0.21 mg/mL, respectively.

  15. Crystal structure of 3-acetyl-4H-chromen-4-one

    Directory of Open Access Journals (Sweden)

    Yoshinobu Ishikawa

    2015-07-01

    Full Text Available In the title compound, C11H8O3, the fused-ring system is almost planar (r.m.s. deviation = 0.020 Å, with the largest deviation from the least-squares plane [0.0462 (17 Å] being for a pyran C atom. The dihedral angle between the plane of the fused-ring system and acetyl plane is 5.149 (16°. In the crystal, the fused rings are linked by aromatic π–π stacking interactions [centroid–centroid distance between the benzene and pyran rings = 3.643 (6 Å] and C—H...O hydrogen bonds, generating a three-dimensional network.

  16. Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents.

    Science.gov (United States)

    El-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; El-Kholy, Yehya M; El-Sayed, Shahenaz H; El-Naggar, Tarek B A

    2011-10-01

    A structurally diverse series of Δ(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC-62 cell line.

  17. A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly

    OpenAIRE

    Xhemalce, Blerta; Kouzarides, Tony

    2010-01-01

    Chromodomain proteins (Chp1/Chp2/Swi6/Clr4) bind to methylated H3K9 (H3K9me) and regulate pericentric heterochromatin in fission yeast. Chp1 and Clr4 (H3K9-HMT), bind transcriptionally active heterochromatin, whereas Chp2/Swi6 (HP1 homologs) are recruited during the inactive state. We show that H3K4 acetylation (H3K4ac) plays a role in the transition of dimethylated H3K9 (H3K9me2) occupancy from Chp1/Clr4 to Chp2/Swi6. H3K4ac, mediated by Mst1, is enriched at pericentromeres concomitantly wit...

  18. Effects of aeration on formation and localization of the acetyl coenzyme A synthetases of Saccharomyces cerevisiae

    Science.gov (United States)

    Klein, H. P.; Jahnke, L.

    1979-01-01

    Previous studies on the yeast Saccharomyces cerevisiae have shown that two different forms of the enzyme acetyl coenzyme A synthetase (ACS) are present, depending on the conditions under which the cells are grown. The paper evaluates the usefulness of a method designed to assay both synthetases simultaneously in yeast homogenates. The data presented confirm the possibility of simultaneous detection and estimation of the amount of both ACSs of S. cerevisiae in crude homogenates of this strain, making possible the study of physiological factors involved in the formation of these isoenzymes. One important factor for specifying which of the two enzymes is found in these yeast cells is the presence or absence of oxygen in their environment. Aeration not only affects the ratio of the two ACSs but also appears to affect the cellular distribution of these enzymes. Most of the data presented suggest the possibility that the nonaerobic ACS may serve as a precursor to the aerobic form.

  19. Periodic Mesoporous Organosilica Functionalized with Sulfonic Acid Groups as Acid Catalyst for Glycerol Acetylation

    Directory of Open Access Journals (Sweden)

    Pascal Van Der Voort

    2013-08-01

    Full Text Available A Periodic Mesoporous Organosilica (PMO functionalized with sulfonic acid groups has been successfully synthesized via a sequence of post-synthetic modification steps of a trans-ethenylene bridged PMO material. The double bond is functionalized via a bromination and subsequent substitution obtaining a thiol functionality. This is followed by an oxidation towards a sulfonic acid group. After full characterization, the solid acid catalyst is used in the acetylation of glycerol. The catalytic reactivity and reusability of the sulfonic acid modified PMO material is investigated. The catalyst showed a catalytic activity and kinetics that are comparable with the commercially available resin, Amberlyst-15, and furthermore our catalyst can be recycled for several subsequent catalytic runs and retains its catalytic activity.

  20. Thermochemical study of 1-acetyl vinyl p-nitrobenzoate: vinyl bond enthalpy in captodative olefins.

    Science.gov (United States)

    Rojas, Aarón; Valdés-Ordoñez, Alejandro; Martínez-Herrera, Melchor; Torres, Luis Alfonso; Campos, Myriam; Hernández-Obregón, Javier; Herrera, Rafael; Tamariz, Joaquín

    2015-05-21

    Captodative olefins are highly reactive and selective substrates in Diels-Alder and 1,3-dipolar cycloadditions. Seeking an explanation of this fact based on molecular energetics, the thermochemical analysis of 1-acetyl vinyl p-nitrobenzoate, a captodative olefin, has been performed using semi-micro-combustion calorimetry, effusion measurements through a quartz crystal microbalance, and differential scanning calorimetry. The molar standard combustion energy and enthalpy as well as the molar standard formation enthalpy are reported along with sublimation and melting enthalpies. From these data, experimental formation enthalpy of the gas-phase is derived and compared with the theoretical value calculated through the density functional theory procedure. The olefinic bond enthalpy is also computed from experimental data, and the relevance of the results is discussed.

  1. Chemicals loading in acetylated bamboo assisted by supercritical CO2 based on phase equilibrium data

    Science.gov (United States)

    Silviana, Petermann, M.

    2015-12-01

    Indonesia has a large tropical forest. However, the deforestation still appears annually and vastly. This reason drives a use of bamboo as wood alternative. Recently, there are many modifications of bamboo in order to prolong the shelf life. Unfortunately, the processes need more chemicals and time. Based on wood modification, esterifying of bamboo was undertaken in present of a dense gas, i.e. supercritical CO2. Calculation of chemicals loading referred to ASTM D1413-99 by using the phase equilibrium data at optimum condition by a statistical design. The results showed that the acetylation of bamboo assisted by supercritical CO2 required 14.73 kg acetic anhydride/m3 of bamboo for a treatment of one hour.

  2. [Epigenetics and drug addiction: a focus on MeCP2 and on histone acetylation].

    Science.gov (United States)

    Zwiller, Jean

    2015-04-01

    Chronic drug exposure alters gene expression in the brain, which is believed to underlie compulsive drug seeking and drug taking behavior. Recent evidence shows that drug-induced long-term neuroadaptations in the brain are mediated in part by epigenetic mechanisms. By remodeling chromatin, this type of regulation contributes to drug-induced synaptic plasticity that translates into behavioral modifications. How drug-induced alterations in DNA methylation regulate gene expression is reviewed here, with a focus on MeCP2, a protein binding methylated DNA. The importance of histone modifications, especially acetylation is also discussed, with an emphasis on the effects of inhibitors of histone deacetylases on drug-induced behavioral changes. The precise identification of the epigenetic mechanisms that are under the control of drugs of abuse may help to uncover novel targets for the treatment of drug seeking and relapse. PMID:25958763

  3. 2-Bromopalmitate modulates neuronal differentiation through the regulation of histone acetylation

    Directory of Open Access Journals (Sweden)

    Xueran Chen

    2014-03-01

    Full Text Available In order to evaluate the functional significance of palmitoylation during multi-potent neural stem/progenitor cell proliferation and differentiation, retinoic acid-induced P19 cells were used in this study as a model system. Cell behaviour was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BP. Here, we observed a significant reduction in neuronal differentiation in the 2BP-treated cell model. We further explored the underlying mechanisms and found that 2BP resulted in the decreased acetylation of histones H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor cells' renewal. Our results established a direct link between palmitoylation and the regulation of neural cell fate specification and revealed the epigenetic regulatory mechanisms that are involved in the effects of palmitoylation during neural development.

  4. Versatile colorant syntheses by multiple condensations of acetyl anilines with perylene anhydrides.

    Science.gov (United States)

    Jänsch, Daniel; Li, Chen; Chen, Long; Wagner, Manfred; Müllen, Klaus

    2015-02-01

    We report a key step forward in rylene chemistry: the transformation of rylenes into novel chromophore families. The imidization of rylene anhydrides with 2-acetyl anilines could be controlled by the choice of the solvent, thus causing a transformation into either a 4-hydroxyquinoline (4-HQ) or a 4-oxoquinoline (4-OQ) unit. The 4-OQ motif contains an aminoenone group formed by intramolecular aldol condensation and is the first vinylogous rylene imide. The concept of vinylogy was further developed by utilizing 2,6-diacetyl aniline leading to an 3a-aza-1,6-phenalenedione-extended rylene skeleton fully embracing the nitrogen atom. By functionalization of the aminoenone motifs, for example, malononitrile addition at the carbonyl groups, the optical and electronic properties could be further tuned. PMID:25586519

  5. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    Directory of Open Access Journals (Sweden)

    Tomohiro Osaki

    2015-08-01

    Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

  6. [Acetyl-CoA cleavage and synthesis in methanogens]. Progress report, September 1994--August 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-11-01

    The acetyl-CoA decarbonylase synthase (ACDS) complex has been detected in a variety of methanogens including species of Methanosarcina, Methanothrix (i.e., Methanosaeta), and Methanococcus. The multienzyme complex from Methanosarcina barkeri is composed of five different subunits, possibly arranged in an {alpha}{sub 6}{beta}{sub 6}{gamma}{sub 6}{delta}{sub 6}{var_epsilon}{sub 6} structure with the individual subunits of molecular masses (kDa) of 89, 60, 50, 48, and 20, respectively. This progress report summarizes the work from the past 21 months on studies directed toward understanding how the ACDS complex functions in the physiology of acetate-cleaving, and acetate-synthesizing methanogens.

  7. Identification of a bacterial pectin acetyl esterase in Erwinia chrysanthemi 3937.

    Science.gov (United States)

    Shevchik, V E; Hugouvieux-Cotte-Pattat, N

    1997-06-01

    Erwinia chrysanthemi causes soft-rot diseases of various plants by enzymatic degradation of the pectin in plant cell walls. The structural complexity of pectin requires the combined action of several pectinases for its efficient breakdown. Three types of pectinases have so far been identified in E. chrysanthemi: two pectin methyl esterases (PemA, PemB), a polygalacturonase (PehX), and eight pectate lyases (PelA, PelB, PelC, PelD, PelE, PelL, PelZ, PelX). We report in this paper the analysis of a novel enzyme, the pectin acetyl esterase encoded by the paeY gene. No bacterial form of pectin acetyl esterases has been described previously, while plant tissues and some pectinolytic fungi were found to produce similar enzymes. The paeY gene is present in a cluster of five pectinase-encoding genes, pelA-pelE-pelD-paeY-pemA. The paeY open reading frame is 1650 bases long and encodes a 551-residue precursor protein of 60704Da, including a 25-amino-acid signal peptide. PaeY shares one region of homology with a rhamnogalacturonan acetyl esterase of Aspergillus aculeatus. To characterize the enzyme, the paeY gene was overexpressed and its protein product was purified. PaeY releases acetate from sugar-beet pectin and from various synthetic substrates. Moreover, the enzyme was shown to act in synergy with other pectinases. The de-esterification rate by PaeY increased after previous demethylation of the pectins by PemA and after depolymerization of the pectin by pectate lyases. In addition, the degradation of sugar-beet pectin by pectate lyases is favoured after the removal of methyl and acetyl groups by PemA and PaeY, respectively. The paeY gene was first identified on the basis of its regulation, which shares several characteristics with that of other pectinases. Analysis of the paeY transcription, using gene fusions, revealed that it is induced by pectic catabolic products and is affected by growth phase, oxygen limitation and catabolite repression. Regulation of pae

  8. Synthesis of (2-pyridyl)-Acetyl Chitosan and Its Antioxidant Activity

    International Nuclear Information System (INIS)

    In this paper, chloracetyl chitosan (CACTS) was prepared at first. In the molecules of CACTS, there are active chlorine groups, which can take part in other reactions. Thus, number of chitosan derivatives will be obtained after chlorine is substituted. Choosing pyridine as the active group, a novel water-soluble chitosan derivative, (2-pyridyl)-acetyl chitosan (PACTS) was obtained and its antioxidant activity against hydroxyl radicals and superoxide radicals was assessed. The results indicated that PACTS had better antioxidant activity than that of chitosan, carboxymethyl chitosan (CMCTS), hydroxypropyl chitosan (HPCTS), and Vitamin C. And the IC50 values against hydroxyl radicals and superoxide radicals were 0.31 mg/mL and 0.21 mg/mL, respectively

  9. Role of acetylation and charge in antimicrobial peptides based on human beta-defensin-3.

    Science.gov (United States)

    Papanastasiou, Emilios Andrew; Hua, Quyen; Sandouk, Aline; Son, U Hyon; Christenson, Andrew James; Van Hoek, Monique Louise; Bishop, Barney Michael

    2009-07-01

    Cationic antimicrobial peptides are an evolutionarily ancient and essential element of innate immunity in higher organisms. The precise mechanism by which these peptides exert their antimicrobial activity on bacteria is not well understood. Decapeptides based on the C-terminus of human beta-defensin-3 were designed and evaluated to study the role of charge in defining the antimicrobial activity and selectivity of these peptides against Escherichia coli. Acetylated derivatives of these peptides were prepared in order to further evaluate how positively charged primary amines contribute to potency in these small antimicrobial peptides. These peptides enabled us to explore the relationship between net charge, charge distribution and antimicrobial activity. While the results indicate that net charge is a major factor in antimicrobial activity in these peptides, the actual relationship between charge and potency appears to be more complex.

  10. Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-β-boswellic acid from Boswellia serrata

    Directory of Open Access Journals (Sweden)

    Arora Daljit S

    2011-03-01

    Full Text Available Abstract Background Boswellic acids are pentacyclic triterpenes, which are produced in plants belonging to the genus Boswellia. Boswellic acids appear in the resin exudates of the plant and it makes up 25-35% of the resin. β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid have been implicated in apoptosis of cancer cells, particularly that of brain tumors and cells affected by leukemia or colon cancer. These molecules are also associated with potent antimicrobial activities. The present study describes the antimicrobial activities of boswellic acid molecules against 112 pathogenic bacterial isolates including ATCC strains. Acetyl-11-keto-β-boswellic acid (AKBA, which exhibited the most potent antibacterial activity, was further evaluated in time kill studies, postantibiotic effect (PAE and biofilm susceptibility assay. The mechanism of action of AKBA was investigated by propidium iodide uptake, leakage of 260 and 280 nm absorbing material assays. Results AKBA was found to be the most active compound showing an MIC range of 2-8 μg/ml against the entire gram positive bacterial pathogens tested. It exhibited concentration dependent killing of Staphylococcus aureus ATCC 29213 up to 8 × MIC and also demonstrated postantibiotic effect (PAE of 4.8 h at 2 × MIC. Furthermore, AKBA inhibited the formation of biofilms generated by S. aureus and Staphylococcus epidermidis and also reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide and leakage of 260 and 280 nm absorbing material by AKBA treated cells of S aureus indicating that the antibacterial mode of action of AKBA probably occurred via disruption of microbial membrane structure. Conclusions This study supported the potential use of AKBA in treating S. aureus infections. AKBA can be further exploited to evolve potential lead compounds in the discovery of new anti-Gram-positive and anti-biofilm agents.

  11. ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.

    Science.gov (United States)

    Clarke, Christopher J; Shamseddine, Achraf A; Jacob, Joseph J; Khalife, Gabrielle; Burns, Tara A; Hannun, Yusuf A

    2016-05-01

    Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels. PMID:27013100

  12. Structure and Reactivity of the N-Acetyl-Cysteine Radical Cation and Anion: Does Radical Migration Occur?

    NARCIS (Netherlands)

    Osburn, S.; G. Berden,; Oomens, J.; O' Hair, R. A. J.; Ryzhov, V.

    2011-01-01

    The structure and reactivity of the N-acetyl-cysteine radical cation and anion were studied using ion-molecule reactions, infrared multi-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The radical cation was generated by first nitrosylating the thiol of N-

  13. Structure and reactivity of the N-acetyl-cysteine radical cation and anion: does radical migration occur?

    NARCIS (Netherlands)

    S. Osburn; G. Berden; J. Oomens; R.A.J. O'Hair; V. Ryzhov

    2011-01-01

    The structure and reactivity of the N-acetyl-cysteine radical cation and anion were studied using ion-molecule reactions, infrared multi-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The radical cation was generated by first nitrosylating the thiol of N-

  14. Hydrolyses of alpha-naphthyl acetate, beta-naphthyl acetate, and acetyl-DL-phenylalanine beta-naphthyl ester

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D

    1983-01-01

    Using simultaneous coupling azo dye techniques kidney enzymes active against alpha-naphthyl acetate, beta-naphthyl acetate, and acetyl-DL-phenylalanine beta-naphthyl ester are characterized. The enzymes show identical distribution in the section. The banding patterns in zymograms are the same after...

  15. N,O6-partially acetylated chitosan nanoparticles hydrophobically-modified for controlled release of steroids and vitamin E

    DEFF Research Database (Denmark)

    Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen;

    2013-01-01

    Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also character...

  16. Synthesis, structural studies and biological activity of new Cu(II) complexes with acetyl derivatives of 7-hydroxy-4-methylcoumarin.

    Science.gov (United States)

    Klepka, Marcin T; Drzewiecka-Antonik, Aleksandra; Wolska, Anna; Rejmak, Paweł; Ostrowska, Kinga; Hejchman, Elżbieta; Kruszewska, Hanna; Czajkowska, Agnieszka; Młynarczuk-Biały, Izabela; Ferenc, Wiesława

    2015-04-01

    The new Cu(II) complexes with 6-acetyl-7-hydroxy-4-methylcoumarin (HL1) and 8-acetyl-7-hydroxy-4-methylcoumarin (HL2) have been obtained by the electrochemical method. The density functional theory calculations and X-ray absorption spectroscopy techniques have been used to geometrically describe a series of new compounds. The studies have been focused on the coordination mode of the hydroxy ligands to the metallic centre. The complexes, Cu(HL1)2 and Cu(HL2)2⋅0.5H2O, have flat square geometry with oxygen atoms in the first coordination sphere. Two bidentate anionic coumarins are bonded to the metal cation via the acetyl and deprotonated hydroxyl O atoms. Biological activity, including microbiological and cytotoxic, has been evaluated and found to be enhanced in comparison with the parent ligands. Moreover, the Cu(II) complex with 8-acetyl-7-hydroxy-4-methylcoumarin shows similar antifungal activity as commercially used fluconazole.

  17. Stability of carboplatin, paclitaxel, and docetaxel with acetyl-l-carnitine during simulated Y-site administration.

    Science.gov (United States)

    Zhang, Yang; Scarlett, Cameron; Hutson, Paul

    2012-01-01

    The compatibility of acetyl-l-carnitine with three chemotherapy agents was studied during simulated Y-site administration. Acetyl-l-carnitine 30 mg/mL in 5% dextrose for injection (D5W) was combined with carboplatin 4 mg/mL, paclitaxel 2 mg/mL, and docetaxel 0.74 mg/mL in glass vials. Physical compatibility over the 4-hour storage at room temperature was assessed by visual examinations with unaided eye under fluorescent light and by measuring the percent transmittance at 600 nm. Chemical compatibility was measured by the percent of initial concentration remaining using stability-indicating high-performance liquid chromatographic-ultraviolet and high-performance liquid chromatographic-mass spectrometry methods. No visible particulate matter, haze, or color change was observed, and the percent transmittance was >95% for all admixtures. After a 4-hour incubation, 93.2% of the paclitaxel and 96.5% of docetaxel remained in separate mixtures with acetyl-l-carnitine. Carboplatin 4 mg/mL, paclitaxel 1.2 mg/mL, and docetaxel 0.74 mg/mL are physically and chemically compatible with acetyl-l-carnitine 30 mg/mLin D5W during a simulated 4-hour Y-site administration. PMID:23050317

  18. An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2

    DEFF Research Database (Denmark)

    Zlocowski, Natacha; Lorenz, Virginia; Bennett, Eric Paul;

    2013-01-01

    Abstract Polypeptide GalNAc-transferases (ppGalNAc-Ts) are a family of enzymes that catalyze the initiation of mucin-type O-glycosylation. All ppGalNAc-T family members contain a common (QXW)3 motif which is present in R-type lectin group. Acetylation site K521 is part of the QKW motif of ß......-trefoil in the lectin domain of ppGalNAc-T2. We used a combination of acetylation and site-directed mutagenesis approaches to examine the functional role of K521 in ppGalNAc-T2. Binding assays of non-acetylated and acetylated forms of the mutant ppGalNAc-T2K521Q to various naked and aGalNAc-glycosylated mucin peptides...... indicated that degree of interaction of lectin domain with aGalNAc depends on the peptide sequence of mucin. Studies of inhibitory effect of various carbohydrates on interactions of ppGalNAc-T2 with MUC1aGalNAc indicate that point K521Q mutation enhance the carbohydrate specificity of lectin domain for aGalNAc...

  19. A multienzyme complex channels substrates and electrons through acetyl-CoA and methane biosynthesis pathways in Methanosarcina.

    Directory of Open Access Journals (Sweden)

    Dillon J Lieber

    Full Text Available Multienzyme complexes catalyze important metabolic reactions in many organisms, but little is known about the complexes involved in biological methane production (methanogenesis. A crosslinking-mass spectrometry (XL-MS strategy was employed to identify proteins associated with coenzyme M-coenzyme B heterodisulfide reductase (Hdr, an essential enzyme in all methane-producing archaea (methanogens. In Methanosarcina acetivorans, Hdr forms a multienzyme complex with acetyl-CoA decarbonylase synthase (ACDS, and F420-dependent methylene-H4MPT reductase (Mer. ACDS is essential for production of acetyl-CoA during growth on methanol, or for methanogenesis from acetate, whereas Mer is essential for methanogenesis from all substrates. Existence of a Hdr:ACDS:Mer complex is consistent with growth phenotypes of ACDS and Mer mutant strains in which the complex samples the redox status of electron carriers and directs carbon flux to acetyl-CoA or methanogenesis. We propose the Hdr:ACDS:Mer complex comprises a special class of multienzyme redox complex which functions as a "biological router" that physically links methanogenesis and acetyl-CoA biosynthesis pathways.

  20. Iodine Supported on 3-Aminopropyl Silica Gel as Efficient Catalyst for Acetylation of Alcohols under Solvent-free Conditions

    Institute of Scientific and Technical Information of China (English)

    MAHDAVI Hossein; GHAEMY Mosa; ZERAATPISHEH Fatemeh

    2009-01-01

    3-Aminopropyl silica gel (I2/APSG) was found to catalyze the acetylation of alcohols and phenols efficiently with acetic anhydride. The reaction is mild and selective with high yields. A wide variety of alcohols and phenols are selectively converted into the corresponding acetates using I2/APSG under solvent-free conditions at room tem-perature.