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https://www.readbyqxmd.com/read/27905930/combinatory-optimization-of-chromosomal-integrated-mevalonate-pathway-for-%C3%AE-carotene-production-in-escherichia-coli
#1
Lijun Ye, Chunzhi Zhang, Changhao Bi, Qingyan Li, Xueli Zhang
BACKGROUND: Plasmid expression is a popular method in studies of MVA pathway for isoprenoid production in Escherichia coli. However, heterologous gene expression with plasmid is often not stable and might burden growth of host cells, decreases cell mass and product yield. In this study, MVA pathway was divided into three modules, and two heterologous modules were integrated into the E. coli chromosome. These modules were individually modulated with regulatory parts to optimize efficiency of the pathway in terms of downstream isoprenoid production...
December 1, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27905068/inhibition-of-mevalonate-pathway-and-synthesis-of-the-storage-lipids-in-human-liver-derived-and-non-liver-cell-lines-by-lippia-alba-essential-oils
#2
Sandra Montero-Villegas, Mónica Polo, Marianela Galle, Boris Rodenak-Kladniew, María Castro, Ana Ves-Losada, Rosana Crespo, Margarita García de Bravo
The essential oils (EOs) of Lippia alba, an herb extensively used as a folk medicine in Latin America, are today promoted as an effective means of eliminating problems caused by hyperlipemia. We hypothesized that L.alba EOs inhibited cholesterol and triacylglycerols synthesis and decreased the intracellular depots of those lipids (lipid droplets), mechanisms involving the induction of a hypolipidemic response. Our aim was, therefore, to evaluate the hypolipogenic capability of the EOs of four L. alba chemotypes on liver-derived (HepG2) and non-liver (A549) human cell lines and to identify the potential biochemical targets of those chemotypes, particularly within the mevalonate pathway (MP)...
November 30, 2016: Lipids
https://www.readbyqxmd.com/read/27886451/activity-of-fluorine-containing-analogues-of-wc-9-and-structurally-related-analogues-against-two-intracellular-parasites-trypanosoma-cruzi-and-toxoplasma-gondii
#3
María N Chao, Catherine Li, Melissa Storey, Bruno N Falcone, Sergio H Szajnman, Sergio M Bonesi, Roberto Docampo, Silvia N J Moreno, Juan B Rodriguez
Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells...
November 25, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27884413/peroxisome-proliferator-activated-receptor-%C3%AE-down-regulation-mediates-the-inhibitory-effect-of-d-%C3%AE-tocotrienol-on-the-differentiation-of-murine-3t3-f442a-preadipocytes
#4
Sheida Torabi, Hoda Yeganehjoo, Chwan-Li Shen, Huanbiao Mo
Tocotrienols accelerate the degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that catalyzes the biosynthesis of mevalonate; the latter is essential for preadipocyte differentiation. Tocotrienols also down-regulate peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation. We hypothesized that mevalonate deprivation and PPARγ down-regulation mediate d-δ-tocotrienol-induced inhibition of adipocyte differentiation. The objectives of this study were to determine the effect of d-δ-tocotrienol on 3T3-F442A preadipocyte differentiation and the involvement of PPARγ and mevalonate...
November 3, 2016: Nutrition Research
https://www.readbyqxmd.com/read/27883036/the-mevalonate-pathway-regulates-primitive-streak-formation-via-protein-farnesylation
#5
Yoshimi Okamoto-Uchida, Ruoxing Yu, Norio Miyamura, Norie Arima, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Suguru Yoshida, Takamitsu Hosoya, Makiko Nawa, Takeshi Kasama, Yoichi Asaoka, Reiner Wimmer Alois, Ulrich Elling, Josef M Penninger, Sachiko Nishina, Noriyuki Azuma, Hiroshi Nishina
The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871246/functional-characterization-of-thiolase-encoding-genes-from-xanthophyllomyces-dendrorhous-and-their-effects-on-carotenoid-synthesis
#6
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/27868197/expression-of-a-hepatitis-b-virus-pre-s2-deletion-mutant-in-the-liver-results-in-hepatomegaly-and-hepatocellular-carcinoma-in-mice
#7
Yuan-Chi Teng, Jenq Chyuan Neo, Jaw-Ching Wu, Yi-Fan Chen, Cheng-Heng Kao, Ting-Fen Tsai
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and has a poor prognosis and a low survival rate; its incidence is on the rise. Hepatitis B virus (HBV) infection is one of the main causes of HCC. A high prevalence of pre-S deletions of HBV surface antigen, which encompass T-cell and/or B-cell epitopes, is found in HBV carriers; antiviral therapy and viral immune escape may cause and select for these HBV mutants. In particular, the presence of pre-S2 deletion mutants is an important risk factor associated with cirrhosis and HCC...
November 21, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27864137/intergenomic-evolution-and-metabolic-cross-talk-between-rumen-and-thermophilic-autotrophic-methanogenic-archaea
#8
M Bharathi, P Chellapandi
Methanobrevibacter ruminantium M1 (MRU) is a rumen methanogenic archaean that can be able to utilize formate and CO2/H2 as growth substrates. Extensive analysis on the evolutionary genomic contexts considered herein to unravel its intergenomic relationship and metabolic adjustment acquired from the genomic content of Methanothermobacter thermautotrophicus ΔH. We demonstrated its intergenomic distance, genome function, synteny homologs and gene families, origin of replication, and methanogenesis to reveal the evolutionary relationships between Methanobrevibacter and Methanothermobacter...
November 15, 2016: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/27864002/gamma-tocotrienol-reverses-multidrug-resistance-of-breast-cancer-cells-with-a-mechanism-distinct-from-that-of-atorvastatin
#9
Yuedi Ding, Ying Peng, Lili Deng, Jun Fan, Biao Huang
In addition to its antioxidant properties, γ-tocotrienol also has the ability to inhibit HMG-CoA reductase, which is the key enzyme in the mevalonate pathway for cholesterol biosynthesis. Statins, the competitive inhibitors of HMG-CoA reductase, display potent anticancer activity and reversal ability of multidrug resistance in a variety of tumor cells, which is believed to be due to their inhibition of HMG-CoA reductase. Here, we determined the role of the mevalonate pathway in γ-tocotrienol-mediated reversal of multidrug resistance in cancer cells...
November 15, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27860262/ferroptosis-a-new-form-of-cell-death-and-its-relationships-with-tumourous-diseases
#10
REVIEW
Haitao Yu, Pengyi Guo, Xiaozai Xie, Yi Wang, Gang Chen
Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system Xc(-) inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e...
November 10, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27856657/the-challenge-of-autoinflammatory-syndromes-with-an-emphasis-on-hyper-igd-syndrome
#11
REVIEW
Jos W M van der Meer, Anna Simon
Autoinflammatory syndromes are disorders with an exaggerated inflammatory response, mostly in the absence of an appropriate trigger. Prototypic autoinflammatory syndromes are FMF, hyper-IgD syndrome (also known as mevalonate kinase deficiency), TNF receptor-associated periodic syndrome and cryopyrin-associated periodic syndrome. The clinical phenotypes partly overlap (with fever and acute phase response), but also differ between the various syndromes (e.g. regarding fever pattern, episodic vs chronic inflammation and accompanying clinical signs)...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27849604/correction-for-wang-et-al-interplay-of-mevalonate-and-hippo-pathways-regulates-rhamm-transcription-via-yap-to-modulate-breast-cancer-cell-motility
#12
(no author information available yet)
No abstract text is available yet for this article.
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27825357/fermentative-production-and-direct-extraction-of-%C3%AE-bisabolol-in-metabolically-engineered-escherichia-coli
#13
Gui Hwan Han, Seong Keun Kim, Paul Kyung-Seok Yoon, Younghwan Kang, Byoung Su Kim, Yaoyao Fu, Bong Hyun Sung, Heung Chae Jung, Dae-Hee Lee, Seon-Won Kim, Seung-Goo Lee
BACKGROUND: (-)-α-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-α-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-α-bisabolol plays a key role in the development of its sustainable production from renewable feedstock...
November 8, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27821871/a-structural-and-functional-study-on-the-2-c-methyl-d-erythritol-4-phosphate-cytidyltransferase-ispd-from-bacillus-subtilis
#14
Yun Jin, Zhongchuan Liu, Yanjie Li, Weifeng Liu, Yong Tao, Ganggang Wang
2-C-Methyl-D-erythritol-4-phosphate cytidyltransferase (IspD) is an essential enzyme in the mevalonate-independent pathway of isoprenoid biosynthesis. This enzyme catalyzes 2-C-Methyl-d-erythritol 4-phosphate (MEP) and cytosine triphosphate (CTP) to 4-diphosphocytidyl-2-C-methyl-d-erythritol (CDPME) and inorganic pyrophosphate (PPi). Bacillus subtilis was a kind of excellent isoprene producer. However, the studies on the key enzymes of MEP pathway in B. subtilis were still absent. In this work, the crystal structures of IspD and IspD complexed with CTP from B...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27811147/development-of-the-autoinflammatory-disease-damage-index-addi
#15
Nienke M Ter Haar, Kim V Annink, Sulaiman M Al-Mayouf, Gayane Amaryan, Jordi Anton, Karyl S Barron, Susanne M Benseler, Paul A Brogan, Luca Cantarini, Marco Cattalini, Alexis-Virgil Cochino, Fabrizio De Benedetti, Fatma Dedeoglu, Adriana A De Jesus, Ornella Della Casa Alberighi, Erkan Demirkaya, Pavla Dolezalova, Karen L Durrant, Giovanna Fabio, Romina Gallizzi, Raphaela Goldbach-Mansky, Eric Hachulla, Veronique Hentgen, Troels Herlin, Michaël Hofer, Hal M Hoffman, Antonella Insalaco, Annette F Jansson, Tilmann Kallinich, Isabelle Koné-Paut, Anna Kozlova, Jasmin B Kuemmerle-Deschner, Helen J Lachmann, Ronald M Laxer, Alberto Martini, Susan Nielsen, Irina Nikishina, Amanda K Ombrello, Seza Ozen, Efimia Papadopoulou-Alataki, Pierre Quartier, Donato Rigante, Ricardo Russo, Anna Simon, Maria Trachana, Yosef Uziel, Angelo Ravelli, Marco Gattorno, Joost Frenkel
OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency...
November 3, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27799356/simvastatin-induced-apoptosis-in-osteosarcoma-cells-a-key-role-of-rhoa-ampk-p38-mapk-signaling-in-antitumor-activity
#16
Walied Kamel, Eiji Sugihara, Hiroyuki Nobusue, Sayaka Yamaguchi-Iwai, Nobuyuki Onishi, Kenta Maki, Yumi Fukuchi, Koichi Matsuo, Akihiro Muto, Hideyuki Saya, Takatsune Shimizu
Osteosarcoma is the most common type of primary bone tumor, novel therapeutic agents for which are urgently needed. To identify such agents, we screened a panel of approved drugs with a mouse model of osteosarcoma. The screen identified simvastatin, which inhibited the proliferation and migration of osteosarcoma cells in vitro. Simvastatin also induced apoptosis in osteosarcoma cells in a manner dependent on inhibition of the mevalonate biosynthetic pathway. It also disrupted the function of the small GTPase RhoA and induced activation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), with AMPK functioning upstream of p38 MAPK...
October 31, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27784901/targeting-mutant-p53-through-the-mevalonate-pathway
#17
William Freed-Pastor, Carol Prives
It is well established that mutant forms of the p53 tumour suppressor acquire pro-oncogenic activities. Inhibition of the mevalonate pathway is now shown to promote degradation of select oncogenic mutant p53 proteins, indicating that destabilization of mutant p53 could be a promising therapeutic strategy.
October 27, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27777393/-pharmacokinetics-of-zoledronic-acid-once-yearly-bisphosphonate-intravenous-infusion
#18
Satoshi Tanaka
Zoledronic acid hydrate(zoledronic acid)is an osteoporosis therapeutic agent which shows the fracture suppression effect with once-yearly intravenous infusion. Although zoledronic acid is quickly disappeared from the blood after intravenous infusion, it is taken into the bone immediately and incorporated into the bone tissue. In addition, zoledronic acid shows the potent suppression effect on bone resorption by inhibiting farnesyl diphosphate synthase of the mevalonate pathway(FPPS)strongly. In vivo study, the single intravenous administration of zoledronic acid to the mature ovariectomized(OVX)rats demonstrated to suppress the decreasing bone strength dose-dependently in 32 weeks, corresponding to more than one year in human...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27775703/dnaja1-controls-the-fate-of-misfolded-mutant-p53-through-the-mevalonate-pathway
#19
Alejandro Parrales, Atul Ranjan, Swathi V Iyer, Subhash Padhye, Scott J Weir, Anuradha Roy, Tomoo Iwakuma
Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member...
October 24, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27773750/statin-suppresses-hippo-pathway-inactivated-malignant-mesothelioma-cells-and-blocks-the-yap-cd44-growth-stimulatory-axis
#20
Kosuke Tanaka, Hirotaka Osada, Yuko Murakami-Tonami, Yoshitsugu Horio, Toyoaki Hida, Yoshitaka Sekido
Malignant mesothelioma (MM) frequently exhibits Hippo signaling pathway inactivation (HPI) mainly due to NF2 and/or LATS2 mutations, which leads to the activation of YAP transcriptional co-activator. Here, we show antitumor effects of statin on MM cells with HPI, through the interplay of the mevalonate and Hippo signaling pathways. Statin attenuated proliferation and migration of MM cells harboring NF2 mutation by accelerating YAP phosphorylation/inactivation. CD44 expression was decreased by statin, in parallel with YAP phosphorylation/inactivation...
October 20, 2016: Cancer Letters
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