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https://www.readbyqxmd.com/read/29674394/acetyl-coa-promotes-glioblastoma-cell-adhesion-and-migration-through-ca-2-nfat-signaling
#1
Joyce V Lee, Corbett T Berry, Karla Kim, Payel Sen, Taehyong Kim, Alessandro Carrer, Sophie Trefely, Steven Zhao, Sully Fernandez, Lauren E Barney, Alyssa D Schwartz, Shelly R Peyton, Nathaniel W Snyder, Shelley L Berger, Bruce D Freedman, Kathryn E Wellen
The metabolite acetyl-coenzyme A (acetyl-CoA) is the required acetyl donor for lysine acetylation and thereby links metabolism, signaling, and epigenetics. Nutrient availability alters acetyl-CoA levels in cancer cells, correlating with changes in global histone acetylation and gene expression. However, the specific molecular mechanisms through which acetyl-CoA production impacts gene expression and its functional roles in promoting malignant phenotypes are poorly understood. Here, using histone H3 Lys27 acetylation (H3K27ac) ChIP-seq (chromatin immunoprecipitation [ChIP] coupled with next-generation sequencing) with normalization to an exogenous reference genome (ChIP-Rx), we found that changes in acetyl-CoA abundance trigger site-specific regulation of H3K27ac, correlating with gene expression as opposed to uniformly modulating this mark at all genes...
April 19, 2018: Genes & Development
https://www.readbyqxmd.com/read/29668854/prostate-cancer-chemoprevention-by-sulforaphane-in-a-preclinical-mouse-model-is-associated-with-inhibition-of-fatty-acid-metabolism
#2
Krishna B Singh, Su-Hyeong Kim, Eun-Ryeong Hahm, Subrata K Pore, Bruce L Jacobs, Shivendra V Singh
Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo...
April 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29588626/epistructured-catechins-egcg-and-ec-facilitate-apoptosis-induction-through-targeting-de-novo-lipogenesis-pathway-in-hepg2-cells
#3
Phuriwat Khiewkamrop, Pattamaphron Phunsomboon, Lysiane Richert, Dumrongsak Pekthong, Piyarat Srisawang
Background: Abnormally high expression of the mammalian de novo lipogenesis (DNL) pathway in various cancer cells promotes cell over-proliferation and resistance to apoptosis. Inhibition of key enzymes in the DNL pathway, namely, ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase (FASN) can increase apoptosis without cytotoxicity to non-cancerous cells, leading to the search for and presentation of novel selective and powerful targets for cancer therapy. Previous studies reported that epistructured catechins, epigallocatechin gallate (EGCG) and epicatechin (EC) exhibit different mechanisms regarding a strong inducer of apoptosis in various cancer cell lines...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29477857/balancing-the-carbon-flux-distributions-between-the-tca-cycle-and-glyoxylate-shunt-to-produce-glycolate-at-high-yield-and-titer-in-escherichia-coli
#4
Yu Deng, Ning Ma, Kangjia Zhu, Yin Mao, Xuetuan Wei, Yunying Zhao
The glyoxylate shunt is a branch of the tricarboxylic acid (TCA) cycle which directly determines the synthesis of glycolate, and the balance between the glyoxylate shunt and TCA cycle is very important for the growth of Escherichia coli. In order to accumulate glycolate at high yield and titer, strategies for over-expressing glycolate pathway enzymes including isocitrate lyase (AceA), isocitrate dehydrogenase kinase/phosphatase (AceK) and glyoxylate reductase (YcdW) were analyzed. The genes encoding these three enzymes were transcribed under the control of promoter pTrc on pTrc99A, to form pJNU-3, which was harbored by strain Mgly1, resulting in strain Mgly13...
February 22, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29449592/first-evidence-for-a-multienzyme-complex-of-lipid-biosynthesis-pathway-enzymes-in-cunninghamella-bainieri
#5
Shuwahida Shuib, Izyanti Ibrahim, Mukram Mohamed Mackeen, Colin Ratledge, Aidil Abdul Hamid
Malic enzyme (ME) plays a vital role in determining the extent of lipid accumulation in oleaginous fungi being the major provider of NADPH for the activity of fatty acid synthase (FAS). We report here the first direct evidence of the existence of a lipogenic multienzyme complex (the lipid metabolon) involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and lipid accumulation phases were prepared by protoplasting and subjected to Blue Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449335/bempedoic-acid-lowers-low-density-lipoprotein-cholesterol-and-attenuates-atherosclerosis-in-low-density-lipoprotein-receptor-deficient-ldlr-and-ldlr-yucatan-miniature-pigs
#6
Amy C Burke, Dawn E Telford, Brian G Sutherland, Jane Y Edwards, Cynthia G Sawyez, P Hugh R Barrett, Roger S Newton, J Geoffrey Pickering, Murray W Huff
OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene targeting has been used to generate Yucatan miniature pigs heterozygous ( LDLR +/- ) or homozygous ( LDLR -/- ) for LDL receptor deficiency (ExeGen)...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#7
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29424136/-improving-glycolic-acid-yield-by-metabolic-engineering-in-escherichia-coli
#8
Ning Ma, Kangjia Zhu, Yin Mao, Yu Deng
Glycolic acid is an important industrial compound. To improve glycolic acid yield, we knocked out ldhA (lactate dehydrogenase) in Escherichia coli MG1655 (DE3) to get the strain Mgly1. Then, we regulated expression levels of isocitrate lyase (aceA), glyoxylic acid reductase (ycdW) and isocitrate dehydrogenase kinase/phosphorylase (aceK) that are key enzymes of glycolate synthesis pathway. The yield of glycolic acid increased to 0.326 g/g glucose (38.3% of the theoretical yield) by overexpressing citrate synthase (gltA)...
February 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29423634/critical-steps-in-carbon-metabolism-affecting-lipid-accumulation-and-their-regulation-in-oleaginous-microorganisms
#9
REVIEW
Marianna Dourou, Dimitra Aggeli, Seraphim Papanikolaou, George Aggelis
Oleaginous microorganisms are able to convert numerous agro-industrial and municipal wastes into storage lipids (single cell oil (SCO)) and are therefore considered as potential biofuel producers. While from an environmental and technological point of view the idea to convert waste materials into fuels is very attractive, the production cost of SCO is not currently competitive to that of conventional oils due to the low productivity of oleaginous microorganisms in combination with the high fermentation cost...
February 8, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29415885/ripk3-promotes-kidney-fibrosis-via-akt-dependent-atp-citrate-lyase
#10
Mitsuru Imamura, Jong-Seok Moon, Kuei-Pin Chung, Kiichi Nakahira, Thangamani Muthukumar, Roman Shingarev, Stefan W Ryter, Augustine Mk Choi, Mary E Choi
Renal fibrosis is a common pathogenic response to injury in chronic kidney disease (CKD). The receptor-interacting protein kinase-3 (RIPK3), a regulator of necroptosis, has been implicated in disease pathogenesis. In mice subjected to unilateral ureteral obstruction-induced (UUO-induced) or adenine diet-induced (AD-induced) renal fibrosis, models of progressive kidney fibrosis, we demonstrate increased kidney expression of RIPK3. Mice genetically deficient in RIPK3 displayed decreased kidney fibrosis and improved kidney function relative to WT mice when challenged with UUO or AD...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29395431/atp-citrate-lyase-a-new-player-linking-skeletal-muscle-metabolism-and-epigenetics
#11
Haisen Li, Vittorio Sartorelli
Intermediates generated in several metabolic processes are used to regulate transcription through covalent histone and DNA modifications. In Cell Reports, Das et al. show that acetyl-coenzyme A (acetyl-CoA) generated by ATP citrate lyase (ACL) is utilized to acetylate histone H3 at MyoD regulatory regions, resulting in increased MyoD expression and improved muscle regeneration after injury.
January 30, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29302304/novel-mechanisms-for-organic-acid-mediated-aluminium-tolerance-in-roots-and-leaves-of-two-contrasting-soybean-genotypes
#12
Shou-Cheng Huang, Shu-Juan Chu, Yu-Min Guo, Ya-Jing Ji, Dong-Qing Hu, Jing Cheng, Gui-Hua Lu, Rong-Wu Yang, Cheng-Yi Tang, Jin-Liang Qi, Yong-Hua Yang
Aluminium (Al) toxicity is one of the most important limiting factors for crop yield in acidic soils. However, the mechanisms that confer Al tolerance still remain largely unknown. To understand the molecular mechanism that confers different tolerance to Al, we performed global transcriptome analysis to the roots and leaves of two contrasting soybean genotypes, BX10 (Al-tolerant) and BD2 (Al-sensitive) under 0 and 50 μM Al3+ treatments, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the expression levels of the genes involved in lipid/carbohydrate metabolism and jasmonic acid (JA)-mediated signalling pathway were highly induced in the roots and leaves of both soybean genotypes...
November 2017: AoB Plants
https://www.readbyqxmd.com/read/29296215/cell-surface-grp78-promotes-tumor-cell-histone-acetylation-through-metabolic-reprogramming-a-mechanism-which-modulates-the-warburg-effect
#13
Udhayakumar Gopal, Salvatore V Pizzo
Acetyl coenzyme A (acetyl-CoA) is essential for histone acetylation, to promote cell proliferation by regulating gene expression. However, the underlying mechanism(s) governing acetylation remains poorly understood. Activated α2 -Macroglobulin (α2 M* ) signals through tumor Cell Surface GRP78 (CS-GRP78) to regulate tumor cell proliferation through multiple signaling pathway. Here, we demonstrate that the α2 M* /CS-GRP78 axis regulates acetyl-CoA synthesis and thus functions as an epigenetic modulator by enhancing histone acetylation in cancer cells...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241530/atp-citrate-lyase-regulates-myofiber-differentiation-and-increases-regeneration-by-altering-histone-acetylation
#14
Suman Das, Frederic Morvan, Giulio Morozzi, Benjamin Jourde, Giulia C Minetti, Peter Kahle, Helene Rivet, Pascale Brebbia, Gauthier Toussaint, David J Glass, Mara Fornaro
ATP citrate lyase (ACL) plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. We report here that ACL silencing impairs myoblast and satellite cell (SC) differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD. Conversely, overexpression of ACL enhances MYOD levels and promotes myogenesis. Myogenesis is dependent on transcriptional but also other mechanisms. We show that ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29230177/effect-of-morinda-citrifolia-noni-enriched-diet-on-hepatic-heat-shock-protein-and-lipid-metabolism-related-genes-in-heat-stressed-broiler-chickens
#15
Joshua Flees, Hossein Rajaei-Sharifabadi, Elizabeth Greene, Lesleigh Beer, Billy M Hargis, Laura Ellestad, Tom Porter, Annie Donoghue, Walter G Bottje, Sami Dridi
Heat stress (HS) has been reported to alter fat deposition in broilers, however the underlying molecular mechanisms are not well-defined. The objectives of the current study were, therefore: (1) to determine the effects of acute (2 h) and chronic (3 weeks) HS on the expression of key molecular signatures involved in hepatic lipogenic and lipolytic programs, and (2) to assess if diet supplementation with dried Noni medicinal plant (0.2% of the diet) modulates these effects. Broilers (480 males, 1 d) were randomly assigned to 12 environmental chambers, subjected to two environmental conditions (heat stress, HS, 35°C vs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29201040/caffeoylquinic-acid-rich-extract-of-aster-glehni-f-schmidt-ameliorates-nonalcoholic-fatty-liver-through-the-regulation-of-ppar-%C3%AE-and-adiponectin-in-apoe-ko-mice
#16
Yong-Jik Lee, Yoo-Na Jang, Yoon-Mi Han, Hyun-Min Kim, Jong-Min Jeong, Min Jeoung Son, Chang Bae Jin, Hyoung Ja Kim, Hong Seog Seo
Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni . Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor δ , 5' adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPAR γ coactivator 1-alpha in liver tissues increased in the groups treated with A...
2017: PPAR Research
https://www.readbyqxmd.com/read/29189708/comparative-analysis-of-soybean-root-proteome-reveals-molecular-basis-of-differential-carboxylate-efflux-under-low-phosphorus-stress
#17
Krishnapriya Vengavasi, Renu Pandey, Gerard Abraham, Ravindra Kumar Yadav
Carboxylate efflux from roots is a crucial and differential response of soybean genotypes to low phosphorus (P) stress. Exudation of carboxylic acids including oxalate, citrate, succinate and fumarate was induced under low P stress, particularly in P-efficient soybean genotypes. Enhancement of root length, surface area and volume further improved P acquisition under low P stress. To understand the molecular basis of carboxylate efflux under low P stress, the root proteome of contrasting genotypes (P-efficient: EC-232019 and P-inefficient: EC-113396) was compared...
November 30, 2017: Genes
https://www.readbyqxmd.com/read/29097205/characterization-of-human-alkb-homolog-1-produced-in-mammalian-cells-and-demonstration-of-mitochondrial-dysfunction-in-alkbh1-deficient-cells
#18
Tina A Müller, Sarah L Struble, Katheryn Meek, Robert P Hausinger
Alkbh1 is a mammalian homolog of the Escherichia coli DNA repair enzyme AlkB, an Fe(II) and 2-oxoglutarate dependent dioxygenase that removes alkyl lesions from DNA bases. The human homolog ALKBH1 has been associated with six different enzymatic activities including DNA, mRNA, or tRNA hydroxylation, cleavage at abasic (AP) sites in DNA, as well as demethylation of histones. The reported cellular roles of this protein reflect the diverse enzymatic activities and include direct DNA repair, tRNA modification, and histone modification...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29089625/modes-of-carbon-fixation-in-an-arsenic-and-co-2-rich-shallow-hydrothermal-ecosystem
#19
Nolwenn Callac, Nicole R Posth, Jayne E Rattray, Kweku K Y Yamoah, Alan Wiech, Magnus Ivarsson, Christoffer Hemmingsson, Stephanos P Kilias, Ariadne Argyraki, Curt Broman, Henrik Skogby, Rienk H Smittenberg, Ernest Chi Fru
The seafloor sediments of Spathi Bay, Milos Island, Greece, are part of the largest arsenic-CO2 -rich shallow submarine hydrothermal ecosystem on Earth. Here, white and brown deposits cap chemically distinct sediments with varying hydrothermal influence. All sediments contain abundant genes for autotrophic carbon fixation used in the Calvin-Benson-Bassham (CBB) and reverse tricaboxylic acid (rTCA) cycles. Both forms of RuBisCO, together with ATP citrate lyase genes in the rTCA cycle, increase with distance from the active hydrothermal centres and decrease with sediment depth...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29049011/-omics-of-food-borne-gastroenteritis-global-proteomic-and-mutagenic-analysis-of-salmonella-enterica-serovar-enteritidis
#20
Aryashree Arunima, Soujanya D Yelamanchi, Chandrashekhar Padhi, Sangeeta Jaiswal, Daniel Ryan, Bhawna Gupta, Gajanan Sathe, Jayshree Advani, Harsha Gowda, T S Keshava Prasad, Mrutyunjay Suar
Salmonella Enteritidis causes food-borne gastroenteritis by the two type three secretion systems (TTSS). TTSS-1 mediates invasion through intestinal lining, and TTSS-2 facilitates phagocytic survival. The pathogens' ability to infect effectively under TTSS-1-deficient background in host's phagocytes is poorly understood. Therefore, pathobiological understanding of TTSS-1-defective nontyphoidal Salmonellosis is highly important. We performed a comparative global proteomic analysis of the isogenic TTSS-1 mutant of Salmonella Enteritidis (M1511) and its wild-type isolate P125109...
October 2017: Omics: a Journal of Integrative Biology
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