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https://www.readbyqxmd.com/read/27912843/the-reduced-concentration-of-citrate-in-cancer-cells-an-indicator-of-cancer-aggressiveness-and-a-possible-therapeutic-target
#1
Icard Philippe, Lincet Hubert
Proliferating cells reduce their oxidative metabolism and rely more on glycolysis, even in the presence of O2 (Warburg effect). This shift in metabolism reduces citrate biosynthesis and diminishes intracellular acidity, both of which promote glycolysis sustaining tumor growth. Because citrate is the donor of acetyl-CoA, its reduced production favors a deacetylation state of proteins favoring resistance to apoptosis and epigenetic changes, both processes contributing to tumor aggressiveness. Citrate levels could be monitored as an indicator of cancer aggressiveness (as already shown in human prostate cancer) and/or could serve as a biomarker for response to therapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27912096/drugging-acat1-for-cancer-therapy
#2
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/27909554/high-maysin-corn-silk-extract-reduces-body-weight-and-fat-deposition-in-c57bl-6j-mice-fed-high-fat-diets
#3
Eun Young Lee, Sun Lim Kim, Hyeon Jung Kang, Myung Hwan Kim, Ae Wha Ha, Woo Kyoung Kim
BACKGROUNG/OBJECTIVES: The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. MATERIALS/METHODS: A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration...
December 2016: Nutrition Research and Practice
https://www.readbyqxmd.com/read/27907035/exendin-4-inhibits-hepatic-lipogenesis-by-increasing-%C3%AE-catenin-signaling
#4
Mi Hae Seo, Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won-Young Lee
The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours...
2016: PloS One
https://www.readbyqxmd.com/read/27902927/antidiabetic-activity-of-ganoderma-lucidum-polysaccharides-f31-down-regulated-hepatic-glucose-regulatory-enzymes-in-diabetic-mice
#5
Chun Xiao, Qingping Wu, Jumei Zhang, Yizhen Xie, Wen Cai, Jianbin Tan
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. MATERIALS AND METHODS: Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice...
November 27, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27898105/chemical-induction-of-hairpin-rnai-molecules-to-silence-vital-genes-in-plant-roots
#6
Siming Liu, John I Yoder
Understanding the functions encoded by plant genes can be facilitated by reducing transcript levels by hairpin RNA (hpRNA) mediated silencing. A bottleneck to this technology occurs when a gene encodes a phenotype that is necessary for cell viability and silencing the gene inhibits transformation. Here we compared the use of two chemically inducible plant promoter systems to drive hpRNA mediated gene silencing in transgenic, hairy roots. We cloned the gene encoding the Yellow Fluorescence Protein (YFP) into the dexamethasone inducible vector pOpOff2 and into the estradiol induced vector pER8...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895709/the-dilemma-for-lipid-productivity-in-green-microalgae-importance-of-substrate-provision-in-improving-oil-yield-without-sacrificing-growth
#7
REVIEW
Kenneth Wei Min Tan, Yuan Kun Lee
Rising oil prices and concerns over climate change have resulted in more emphasis on research into renewable biofuels from microalgae. Unlike plants, green microalgae have higher biomass productivity, will not compete with food and agriculture, and do not require fertile land for cultivation. However, microalgae biofuels currently suffer from high capital and operating costs due to low yields and costly extraction methods. Microalgae grown under optimal conditions produce large amounts of biomass but with low neutral lipid content, while microalgae grown in nutrient starvation accumulate high levels of neutral lipids but are slow growing...
2016: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/27895387/retention-of-acetylcarnitine-in-chronic-kidney-disease-causes-insulin-resistance-in-skeletal-muscle
#8
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/27890529/mass-spectrometry-analysis-shows-the-biosynthetic-pathways-supported-by-pyruvate-carboxylase-in-highly-invasive-breast-cancer-cells
#9
Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, Melissa J Longacre, Khanti Rattanapornsompong, Charles F Burant, Sarawut Jitrapakdee, Michael J MacDonald
We recently showed that the anaplerotic enzyme pyruvate carboxylase (PC) is up-regulated in human breast cancer tissue and its expression is correlated with the late stages of breast cancer and tumor size [Phannasil et al., PloS One 10, e0129848, 2015]. In the current study we showed that PC enzyme activity is much higher in the highly invasive breast cancer cell line MDA-MB-231 than in less invasive breast cancer cell lines. We generated multiple stable PC knockdown cell lines from the MDA-MB-231 cell line and used mass spectrometry with (13)C6-glucose and (13)C5-glutamine to discern the pathways that use PC in support of cell growth...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27889747/alisol-a-24-acetate-prevents-hepatic-steatosis-and-metabolic-disorders-in-hepg2-cells
#10
Lu Zeng, WaiJiao Tang, JinJin Yin, LiJuan Feng, Yabing Li, Xiaorui Yao, BenJie Zhou
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model...
November 25, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27887640/functional-and-regulatory-profiling-of-energy-metabolism-in-fission-yeast
#11
Michal Malecki, Danny A Bitton, Maria Rodríguez-López, Charalampos Rallis, Noelia Garcia Calavia, Graeme C Smith, Jürg Bähler
BACKGROUND: The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. RESULTS: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth...
November 25, 2016: Genome Biology
https://www.readbyqxmd.com/read/27887615/developing-a-set-of-strong-intronic-promoters-for-robust-metabolic-engineering-in-oleaginous-rhodotorula-rhodosporidium-yeast-species
#12
Yanbin Liu, Sihui Amy Yap, Chong Mei John Koh, Lianghui Ji
BACKGROUND: Red yeast species in the Rhodotorula/Rhodosporidium genus are outstanding producers of triacylglyceride and cell biomass. Metabolic engineering is expected to further enhance the productivity and versatility of these hosts for the production of biobased chemicals and fuels. Promoters with strong activity during oil-accumulation stage are critical tools for metabolic engineering of these oleaginous yeasts. RESULTS: The upstream DNA sequences of 6 genes involved in lipid biosynthesis or accumulation in Rhodotorula toruloides were studied by luciferase reporter assay...
November 25, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27874312/momilactone-b-inhibits-ketosis-in-vitro-by-regulating-the-angptl3-lpl-pathway-and-inhibiting-hmgcs2
#13
Dong Young Kang, Nipin S P, Pramod Darvin, Youn Hee Joung, Hyo Joo Byun, Chang Hee Do, Kyung Do Park, Mi Na Park, Kwang Hyun Cho, Young Mok Yang
Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis...
November 22, 2016: Animal Biotechnology
https://www.readbyqxmd.com/read/27874045/morphological-and-proteomic-analysis-of-biofilms-from-the-antarctic-archaeon-halorubrum-lacusprofundi
#14
Y Liao, T J Williams, J Ye, J Charlesworth, B P Burns, A Poljak, M J Raftery, R Cavicchioli
Biofilms enhance rates of gene exchange, access to specific nutrients, and cell survivability. Haloarchaea in Deep Lake, Antarctica, are characterized by high rates of intergenera gene exchange, metabolic specialization that promotes niche adaptation, and are exposed to high levels of UV-irradiation in summer. Halorubrum lacusprofundi from Deep Lake has previously been reported to form biofilms. Here we defined growth conditions that promoted the formation of biofilms and used microscopy and enzymatic digestion of extracellular material to characterize biofilm structures...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873387/physical-exercise-remodels-visceral-adipose-tissue-and-mitochondrial-lipid-metabolism-in-rats-fed-a-high-fat-diet
#15
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Sara Becerril, Beatriz Ramírez, I O Gonçalves, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague Dawley rats (6 wks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27872580/untargeted-polar-metabolomics-of-transformed-mda-mb-231-breast-cancer-cells-expressing-varying-levels-of-human-arylamine-n-acetyltransferase-1
#16
Samantha M Carlisle, Patrick J Trainor, Xinmin Yin, Mark A Doll, Marcus W Stepp, J Christopher States, Xiang Zhang, David W Hein
INTRODUCTION: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. Expression of NAT1 is elevated in several cancers including breast cancer. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. OBJECTIVE: This study explored polar metabolome differences between MDA-MB-231 breast cancer cells expressing varying levels of NAT1 activity using an untargeted approach...
July 2016: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/27871246/functional-characterization-of-thiolase-encoding-genes-from-xanthophyllomyces-dendrorhous-and-their-effects-on-carotenoid-synthesis
#17
Nicole Werner, Melissa Gómez, Marcelo Baeza, Víctor Cifuentes, Jennifer Alcaíno
BACKGROUND: The basidiomycetous yeast Xanthophyllomyces dendrorhous has been described as a potential biofactory for terpenoid-derived compounds due to its ability to synthesize astaxanthin. Functional knowledge of the genes involved in terpenoid synthesis would create opportunities to enhance carotenoid production. A thiolase enzyme catalyzes the first step in terpenoid synthesis. RESULTS: Two potential thiolase-encoding genes were found in the yeast genome; bioinformatically, one was identified as an acetyl-CoA C-acetyltransferase (ERG10), and the other was identified as a 3-ketoacyl Co-A thiolase (POT1)...
November 21, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27867161/departure-from-optimal-o2-level-for-mouse-trophoblast-stem-cell-proliferation-and-potency-leads-to-most-rapid-ampk-activation
#18
Yu Yang, Zhongliang Jiang, Alan Bolnick, Jing Dai, Elizabeth E Puscheck, Daniel A Rappolee
Previous studies showed that cultured mouse trophoblast stem cells (mTSCs) have the most rapid proliferation, normal maintenance of stemness/potency, the least spontaneous differentiation, and the lowest level of stress-activated protein kinase (SAPK) when incubated at 2% O2 rather than at the traditional 20% O2 or hypoxic (0.5% and 0% O2) conditions. Switching from 2% O2 induced fast SAPK responses. Here we tested the dose response of AMP-activated protein kinase (AMPK) in its active form (pAMPK Thr172P) at O2 levels from 20-0%, and also tested whether pAMPK levels show similar rapid changes when mTSC cultures were switched from the optimal 2% O2 to other O2 conditions...
November 18, 2016: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/27867011/tetrameric-acetyl-coa-acetyltransferase-1-is-important-for-tumor-growth
#19
Jun Fan, Ruiting Lin, Siyuan Xia, Dong Chen, Shannon E Elf, Shuangping Liu, Yaozhu Pan, Haidong Xu, Zhiyu Qian, Mei Wang, Changliang Shan, Lu Zhou, Qun-Ying Lei, Yuancheng Li, Hui Mao, Benjamin H Lee, Jessica Sudderth, Ralph J DeBerardinis, Guojing Zhang, Taofeek Owonikoko, Manila Gaddh, Martha L Arellano, Hanna J Khoury, Fadlo R Khuri, Sumin Kang, Paul W Doetsch, Sagar Lonial, Titus J Boggon, Walter J Curran, Jing Chen
Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27866253/characterization-of-clostridium-ljungdahlii-ota1-a-non-autotrophic-hyper-ethanol-producing-strain
#20
Jason M Whitham, Mark J Schulte, Benjamin G Bobay, Jose M Bruno-Barcena, Mari S Chinn, Michael C Flickinger, Joel J Pawlak, Amy M Grunden
A Clostridium ljungdahlii lab-isolated spontaneous-mutant strain, OTA1, has been shown to produce twice as much ethanol as the C. ljungdahlii ATCC 55383 strain when cultured in a mixotrophic medium containing fructose and syngas. Whole-genome sequencing identified four unique single nucleotide polymorphisms (SNPs) in the C. ljungdahlii OTA1 genome. Among these, two SNPs were found in the gene coding for AcsA and HemL, enzymes involved in acetyl-CoA formation from CO/CO2. Homology models of the respective mutated enzymes revealed alterations in the size and hydrogen bonding of the amino acids in their active sites...
November 19, 2016: Applied Microbiology and Biotechnology
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