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https://www.readbyqxmd.com/read/27913964/intracerebroventricular-streptozotocin-as-a-model-of-alzheimer-s-disease-neurochemical-and-behavioral-characterization-in-mice
#1
Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Rosana Camarini, Marina Sorrentino Hernandes, Luiz Roberto Britto
Streptozotocin has been widely used to mimic some aspects of Alzheimer's disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice...
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913587/suppressing-n-acetyl-l-aspartate-naa-synthesis-prevents-loss-of-neurons-in-a-murine-model-of-canavan-leukodystrophy
#2
Jiho Sohn, Peter Bannerman, Fuzheng Guo, Travis Burns, Laird Miers, Christopher Croteau, Naveen K Singhal, Jennifer A McDonough, David Pleasure
Canavan disease is a leukodystrophy caused by aspartoacylase (ASPA) deficiency. The lack of functional ASPA, an enzyme enriched in oligodendroglia that cleaves N-acetyl-L-aspartate (NAA) to acetate and L-aspartic acid, elevates brain NAA and causes "spongiform" vacuolation of superficial brain white matter and neighboring gray matter. In children with Canavan disease, neuroimaging shows early-onset dysmyelination and progressive brain atrophy. Neuron loss has been documented at autopsy in some cases. Prior studies have shown that mice homozygous for the Aspa nonsense mutation Nur7 also develop brain vacuolation...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913583/epigenetic-control-of-microsomal-prostaglandin-e-synthase-1-by-hdac-mediated-recruitment-of-p300
#3
Christian Fork, Andrea E Vasconez, Patrick Janetzko, Carlo Angioni, Yannick Schreiber, Nerea Ferreiros, Gerd Geisslinger, Matthias S Leisegang, Dieter Steinhilber, Ralf P Brandes
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medicine to treat pain, fever, inflammation and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. Inhibition of HDACs (HDACi) with the pan HDAC inhibitor SAHA attenuated prostaglandin E2 (PGE2) generation in the murine vasculature and in human vascular smooth muscle cells...
December 2, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27912841/plasmid-mediated-quinolone-resistance-two-decades-on
#4
REVIEW
José Manuel Rodríguez-Martínez, Jesús Machuca, María Eliecer Cano, Jorge Calvo, Luis Martínez-Martínez, Alvaro Pascual
After two decades of the discovery of plasmid-mediated quinolone resistance (PMQR), three different mechanisms have been associated to this phenomenon: target protection (Qnr proteins, including several families with multiple alleles), active efflux pumps (mainly QepA and OqxAB pumps) and drug modification [AAC(6')-Ib-cr acetyltransferase]. PMQR genes are usually associated with mobile or transposable elements on plasmids, and, in the case of qnr genes, are often incorporated into sul1-type integrons. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912096/drugging-acat1-for-cancer-therapy
#5
Javier Garcia-Bermudez, Kivanç Birsoy
In this issue, Fan et al. (2016) show that oncogenic tyrosine kinases can promote glycolysis by phosphorylating and stabilizing the tetrameric form of mitochondrial acetyl-coA acetyltransferase 1 (ACAT1). The authors further identify a small molecule ACAT1 inhibitor that displays anti-cancer effects.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27910960/unc-5-homolog-b-unc5b-is-one-of-the-key-downstream-targets-of-n-%C3%AE-acetyltransferase-10-naa10
#6
Huiyu Xu, Yong Han, Bing Liu, Rong Li
N-α-acetyltransferase 10 (Naa10) displays alpha (N-terminal) acetyltransferase activity. It functions as a major modulator of cell growth and differentiation. Until now, a few downstream targets were found, but no studies have concerned about which gene is the early event of Naa10 downstream target. As we know, the earlier events may play more significant role in Naa10 pathway. Through construction of Naa10 stably knocked down H1299 cell line, we discovered cell morphological changes induced by Naa10. Moreover, potential function of Naa10 in cell morphogenesis was also indicated using cDNA microarray analysis of the Naa10 stably knock-down cell line...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#7
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
December 2, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27909858/distribution-and-morphology-of-cholinergic-cells-in-the-branchial-epithelium-of-zebrafish-danio-rerio
#8
Peter C Zachar, Wen Pan, Michael G Jonz
Acetylcholine is an excitatory neurotransmitter important for oxygen sensing in mammals. A cholinergic mechanism in the fish gill has been implicated in the hyperventilatory response to acute hypoxia; however, the identity and distribution of acetylcholine-containing cells in the gills is poorly defined. We test the hypothesis that cholinergic cells are present in the gill filament epithelium in zebrafish (Danio rerio), a model vertebrate for which oxygen chemoreceptors are well characterized, and that these cells would receive nervous innervation...
December 2, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27904663/t-type-calcium-channel-blocker-attenuates-unilateral-ureteral-obstruction-induced-renal-interstitial-fibrosis-by-activating-the-nrf2-antioxidant-pathway
#9
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Hye Eun Yoon, Ho-Shik Kim, Cheol Whee Park, Yoon Sik Chang, Seok Joon Shin
Besides its effect on high blood pressure, T-type calcium channel blocker is renoprotective in experimental models of renal fibrosis. However, the exact mechanism of T-type calcium channel blocker on tubulointerstitial fibrosis is unclear. We investigated whether the renoprotective effect of T-type calcium channel blocker is associated with modulation of the signaling of oxidative stress-induced renal fibrosis. Treatment with a non-hypotensive dose of efonidipine, a T-type calcium channel blocker, or nifedipine, an L-type channel blocker, was initiated one day before unilateral ureteral obstruction (UUO) in C57BL6/J mice, and was continued until 3 and 7 days after UUO...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903907/chromatin-binding-of-gcn5-in-drosophila-is-largely-mediated-by-cp190
#10
Tamer Ali, Marcus Krüger, Sabin Bhuju, Michael Jarek, Marek Bartkuhn, Rainer Renkawitz
Centrosomal 190 kDa protein (CP190) is a promoter binding factor, mediates long-range interactions in the context of enhancer-promoter contacts and in chromosomal domain formation. All Drosophila insulator proteins bind CP190 suggesting a crucial role in insulator function. CP190 has major effects on chromatin, such as depletion of nucleosomes, high nucleosomal turnover and prevention of heterochromatin expansion. Here, we searched for enzymes, which might be involved in CP190 mediated chromatin changes. Eighty percent of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identified-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#11
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
November 30, 2016: Genome Research
https://www.readbyqxmd.com/read/27901475/spermidine-spermine-n1-acetyltransferase-regulates-cell-growth-and-metastasis-via-akt-%C3%AE-catenin-signaling-pathways-in-hepatocellular-and-colorectal-carcinoma-cells
#12
Cong Wang, Ping Ruan, Ying Zhao, Xiaomin Li, Jun Wang, Xiaoxiao Wu, Tong Liu, Shasha Wang, Jiuzhou Hou, Wei Li, Qian Li, Jinghua Li, Fujun Dai, Dong Fang, Chaojie Wang, Songqiang Xie
Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Therefore, identifying the potential molecular mechanisms that promote HCC and CRC progression and metastasis are urgently needed. Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic enzyme that acetylates the high-order polyamines spermine and spermidine, thus decreasing the cellular content of polyamines. Several publications have suggested that depletion of intracellular polyamines inhibited tumor progression and metastasis in various cancer cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899560/not5-dependent-co-translational-assembly-of-ada2-and-spt20-is-essential-for-functional-integrity-of-saga
#13
Sari Kassem, Zoltan Villanyi, Martine A Collart
Acetylation of histones regulates gene expression in eukaryotes. In the yeast Saccharomyces cerevisiae it depends mainly upon the ADA and SAGA histone acetyltransferase complexes for which Gcn5 is the catalytic subunit. Previous screens have determined that global acetylation is reduced in cells lacking subunits of the Ccr4-Not complex, a global regulator of eukaryotic gene expression. In this study we have characterized the functional connection between the Ccr4-Not complex and SAGA. We show that SAGA mRNAs encoding a core set of SAGA subunits are tethered together for co-translational assembly of the encoded proteins...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899423/myc-mediates-mrna-cap-methylation-of-canonical-wnt-beta-catenin-signaling-transcripts-by-recruiting-cdk7-and-rna-methyltransferase
#14
Valeriya Posternak, Matthew H Ung, Chao Cheng, Michael D Cole
: MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/beta-catenin signaling...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27898394/mef2-transcription-factors-are-key-regulators-of-sprouting-angiogenesis
#15
Natalia Sacilotto, Kira M Chouliaras, Leonid L Nikitenko, Yao Wei Lu, Martin Fritzsche, Marsha D Wallace, Svanhild Nornes, Fernando García-Moreno, Sophie Payne, Esther Bridges, Ke Liu, Daniel Biggs, Indrika Ratnayaka, Shane P Herbert, Zoltán Molnár, Adrian L Harris, Benjamin Davies, Gareth L Bond, George Bou-Gharios, John J Schwarz, Sarah De Val
Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of the endothelium. However, the molecular links between proangiogenic signals and downstream gene expression remain unclear. During sprouting angiogenesis, the specification of endothelial cells into the tip cells that lead new blood vessel sprouts is coordinated by vascular endothelial growth factor A (VEGFA) and Delta-like ligand 4 (Dll4)/Notch signaling and requires high levels of Notch ligand DLL4...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27895387/retention-of-acetylcarnitine-in-chronic-kidney-disease-causes-insulin-resistance-in-skeletal-muscle
#16
Yasunori Miyamoto, Teruo Miyazaki, Akira Honda, Homare Shimohata, Kouichi Hirayama, Masaki Kobayashi
Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27893709/identification-of-myst3-as-a-novel-epigenetic-activator-of-er%C3%AE-frequently-amplified-in-breast-cancer
#17
L Yu, Y Liang, X Cao, X Wang, H Gao, S-Y Lin, R Schiff, X-S Wang, K Li
Estrogen receptor α (ERα) is a master driver of a vast majority of breast cancers. Breast cancer cells often develop resistance to endocrine therapy via restoration of the ERα activity through survival pathways. Thus identifying the epigenetic activator of ERα that can be targeted to block ERα gene expression is a critical topic of endocrine therapy. Here, integrative genomic analysis identified MYST3 as a potential oncogene target that is frequently amplified in breast cancer. MYST3 is involved in histone acetylation via its histone acetyltransferase domain (HAT) and, as a result, activates gene expression by altering chromatin structure...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27891695/downregulation-of-neuronal-vasoactive-intestinal-polypeptide-in-parkinson-s-disease-and-chronic-constipation
#18
F Giancola, F Torresan, R Repossi, F Bianco, R Latorre, A Ioannou, M Guarino, U Volta, P Clavenzani, M Mazzoni, R Chiocchetti, F Bazzoli, R A Travagli, C Sternini, R De Giorgio
BACKGROUND: Chronic constipation (CC) is a common and severe gastrointestinal complaint in Parkinson's disease (PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls...
November 27, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27891321/protective-immunity-elicited-by-oral-immunization-of-mice-with-salmonella-enterica-serovar-typhimurium-braun-lipoprotein-lpp-and-acetyltransferase-msbb-mutants
#19
Tatiana E Erova, Michelle L Kirtley, Eric C Fitts, Duraisamy Ponnusamy, Wallace B Baze, Jourdan A Andersson, Yingzi Cong, Bethany L Tiner, Jian Sha, Ashok K Chopra
We evaluated the extent of attenuation and immunogenicity of the ΔlppAB and ΔlppAB ΔmsbB mutants of Salmonella enterica serovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and triggered robust innate and adaptive immune responses. Comparable levels of IgG and its isotypes were produced in mice infected with wild-type (WT) S...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27890795/inhibition-of-histone-lysine-acetyltransferase-activity-kills-cocl2-treated-and-hypoxia-exposed-gastric-cancer-cells-and-reduces-their-invasiveness
#20
Suvasmita Rath, Lopamudra Das, Shrikant Babanrao Kokate, Nilabh Ghosh, Pragyesh Dixit, Niranjan Rout, Shivaram P Singh, Subhasis Chattopadhyay, Hassan Ashktorab, Duane T Smoot, Mahadeva M Swamy, Tapas K Kundu, Sheila E Crowe, Asima Bhattacharyya
Hypoxia enhances immortality and metastatic properties of solid tumors. Deregulation of histone acetylation has been associated with several metastatic cancers but its effect on hypoxic responses of cancer cells is not known. This study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A, an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter, mitochondrial apoptotic events...
November 23, 2016: International Journal of Biochemistry & Cell Biology
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