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https://www.readbyqxmd.com/read/28544034/knock-down-of-farnesyl-pyrophosphate-synthase-protects-heart-derived-h9c2-cells-against-hypoxia-reoxygenation-induced-injury
#1
Dong-Pu Dai, Huan-Dong Wu, Jian Yang, Shi-Zhen Shen, Chen-Ze Zhao, Jie Ding, Shen-Jiang Hu
Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. Our previous studies have indicated that cardiac-specific overexpression of FPPS induces cardiac hypertrophy and dysfunction in mice, and inhibition of FPPS prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. However, the role for FPPS in myocardial ischemia/reperfusion (MIR) injury is still not clear. The objective of this work was to investigate the effect of FPPS on MIR injury in H9c2 cells which were subjected to hypoxia/reoxygenation (HR) to mimic MIR...
May 24, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28542128/hmg-coa-reductase-promotes-protein-prenylation-and-therefore-is-indispensible-for-t-cell-survival
#2
Sonja M Lacher, Julia Bruttger, Bettina Kalt, Jean Berthelet, Krishnaraj Rajalingam, Simone Wörtge, Ari Waisman
Statins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28532507/isoprenoid-biosynthesis-in-dandelion-latex-is-enhanced-by-the-overexpression-of-three-key-enzymes-involved-in-the-mevalonate-pathway
#3
Katharina M Pütter, Nicole van Deenen, Kristina Unland, Dirk Prüfer, Christian Schulze Gronover
BACKGROUND: Latex from the dandelion species Taraxacum brevicorniculatum contains many high-value isoprenoid end products, e.g. triterpenes and polyisoprenes such as natural rubber. The isopentenyl pyrophosphate units required as precursors for these isoprenoids are provided by the mevalonate (MVA) pathway. The key enzyme in this pathway is 3-hydroxy-methyl-glutaryl-CoA reductase (HMGR) and its activity has been thoroughly characterized in many plant species including dandelion. However, two enzymes acting upstream of HMGR have not been characterized in dandelion latex: ATP citrate lyase (ACL), which provides the acetyl-CoA utilized in the MVA pathway, and acetoacetyl-CoA thiolase (AACT), which catalyzes the first step in the pathway to produce acetoacetyl-CoA...
May 22, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28529155/metabolic-insights-into-the-cold-survival-strategy-and-overwintering-of-the-common-cutworm-spodoptera-litura-fabricius-lepidoptera-noctuidae
#4
Wei Zhu, Huan Zhang, Qian Meng, Menglong Wang, Guiling Zhou, Xuan Li, Hongtuo Wang, Lin Miao, Qilian Qin, Jihong Zhang
The common cutworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), is a destructive pest in Asia. Although overwintering in the field has not been reported for this species, their larvae are capable of long-term survival in fluctuating temperatures, i.e., 5°C (12 h) plus 13°C (12 h), if food is available. With an increase in climate change due to global warming and the widespread use of greenhouses, further understanding of their cold survival strategy is needed to predict and control their population in the future...
May 18, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28524155/statin-use-candidate-mevalonate-pathway-biomarkers-and-colon-cancer-survival-in-a-population-based-cohort-study
#5
Ronan T Gray, Maurice B Loughrey, Peter Bankhead, Chris R Cardwell, Stephen McQuaid, Roisin F O'Neill, Kenneth Arthur, Victoria Bingham, Claire McGready, Anna T Gavin, Jacqueline A James, Peter W Hamilton, Manuel Salto-Tellez, Liam J Murray, Helen G Coleman
BACKGROUND: Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. METHODS: The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522199/engineering-metabolic-pathways-in-escherichia-coli-for-constructing-a-microbial-chassis-for-biochemical-production
#6
REVIEW
Takuya Matsumoto, Tsutomu Tanaka, Akihiko Kondo
The present work reviews literature describing the re-design of the metabolic pathways of a microbial host using sophisticated genetic tools, yielding strains for producing value-added chemicals including fuels, building-block chemicals, pharmaceuticals, and derivatives. This work employed Escherichia coli, a well-studied microorganism that has been successfully engineered to produce various chemicals. E. coli has several advantages compared with other microorganisms, including robustness, and handling. To achieve efficient productivities of target compounds, an engineered E...
May 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28501379/metabolic-impact-of-nutrient-starvation-in-mevalonate-producing-escherichia-coli
#7
Ami Masuda, Yoshihiro Toya, Hiroshi Shimizu
The aim of this work was to enhance mevalonate yield from glucose in Escherichia coli by essential nutrient starvations and to reveal these effects on the central carbon metabolism. Stationary phase culture without essential nutrients such as nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation resulted in the highest mevalonate yield of 0.61C-molC-mol(-1) from glucose. The metabolic impacts of nutrient starvation were investigated by (13)C-metabolic flux analysis...
May 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28501347/defective-protein-prenylation-is-a-diagnostic-biomarker-of-mevalonate-kinase-deficiency
#8
Marcia A Munoz, Julie Jurczyluk, Sam Mehr, Ryan C Chai, Rob J W Arts, Angela Sheu, Chelsea McMahon, Jacqueline R Center, Davinder Singh-Grewal, Jeffrey Chaitow, Dianne E Campbell, Julian M W Quinn, Kirill Alexandrov, Zakir Tnimov, Stuart G Tangye, Anna Simon, Tri Giang Phan, Michael J Rogers
No abstract text is available yet for this article.
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28500274/combined-hmg-coa-reductase-and-prenylation-inhibition-in-treatment-of-ccm
#9
Sayoko Nishimura, Ketu Mishra-Gorur, JinSeok Park, Yulia V Surovtseva, Said M Sebti, Andre Levchenko, Angeliki Louvi, Murat Gunel
Cerebral cavernous malformations (CCMs) are common vascular anomalies that develop in the central nervous system and, more rarely, the retina. The lesions can cause headache, seizures, focal neurological deficits, and hemorrhagic stroke. Symptomatic lesions are treated according to their presentation; however, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. We performed a high-throughput screen to identify Food and Drug Administration-approved drugs or other bioactive compounds that could effectively suppress hyperproliferation of mouse brain primary astrocytes deficient for CCM3...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28497352/monogenic-periodic-fever-syndromes-treatment-options-for-the-pediatric-patient
#10
REVIEW
Seza Ozen, Selcan Demir
Autoinflammatory diseases are disorders of the innate immune system characterized by uncontrolled inflammation. The most commonly encountered autoinflammatory diseases are the hereditary periodic fever syndromes, which present with fever and other features of the skin, serosal membranes, and musculoskeletal system. The main inherited (monogenic) periodic fever syndromes are familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD)...
May 11, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28484475/de-novo-sequencing-and-transcriptome-analysis-reveal-key-genes-regulating-steroid-metabolism-in-leaves-roots-adventitious-roots-and-calli-of-periploca-sepium-bunge
#11
Jian Zhang, Xinglin Li, Fuping Lu, Shanying Wang, Yunhe An, Xiaoxing Su, Xiankuan Li, Lin Ma, Guangjian Han
Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28469419/an-insight-into-structure-function-and-expression-analysis-of-3-hydroxy-3-methylglutaryl-coa-reductase-of-cymbopogon-winterianus
#12
Kamalakshi Devi, Lochana Patar, Mahendra K Modi, Priyabrata Sen
Citronella (Cymbopogon winterianus) is one of the richest sources of high-value isoprenoid aromatic compounds used as flavour, fragrance, and therapeutic elements. These isoprenoid compounds are synthesized by 2 independent pathways: mevalonate pathway and 2-C-methyl-d-erythritol-4-phosphate pathway. Evidence suggests that 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a rate-controlling enzyme for the synthesis of variety of isoprenoids. This study reports the isolation, characterization, and tissue-specific expression analysis of HMGR from citronella...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28454210/statins-and-pancreatic-cancer
#13
Jun Gong, Esha Sachdev, Lori A Robbins, Emily Lin, Andrew E Hendifar, Monica M Mita
Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28442346/identification-of-enzymes-involved-in-the-mevalonate-pathway-of-flavobacterium-johnsoniae
#14
Hajime Hayakawa, Fumiaki Sobue, Kento Motoyama, Tohru Yoshimura, Hisashi Hemmi
The mevalonate pathway is prevalent in eukaryotes, archaea, and a limited number of bacteria. This pathway yields the fundamental precursors for isoprenoid biosynthesis, i.e., isopentenyl diphosphate and dimethylally diphosphate. In the downstream part of the general eukaryote-type mevalonate pathway, mevalonate is converted into isopentenyl diphosphate by the sequential actions of mevalonate kinase, phosphomevalonate kinase, and diphosphomevalonte decarboxylase, while a partial lack of the putative genes of these enzymes is sometimes observed in archaeal and bacterial genomes...
April 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440359/ultrasonographic-findings-in-hyperimmunoglobulin-d-syndrome-a-case-report
#15
Laura Otilia Damian, Otilia Fufezan, Mihaela Farcău, Simona Tătar, Călin Lazăr, Dorin-Ioan Farcău
Hyperimmunoglobulin D syndrome due to mevalonate kinase deficiency is a rare autoinflammatory disease with digestive tract involvement. We report an 11-year female child who has presented since the age of 1 year, bouts of fever, rash, joint swelling, pulmonary consolidation, lymph node involvement and hepatosplenomegaly. Hyperimmunglobulin D and increased urinary mevalonic acid were detected. The ultrasonographic features of hepatosplenomegaly ranged from increment in size to pseudotumoral involvement, with hypoechogenic masses without apparent wall...
April 22, 2017: Medical Ultrasonography
https://www.readbyqxmd.com/read/28440195/editorial-new-insights-into-a-classical-pathway-key-roles-of-the-mevalonate-cascade-in-different-diseases-part-ii
#16
EDITORIAL
Amir A Zeki, Behzad Yeganeh, Nicholas J Kenyon, Saeid Ghavami
No abstract text is available yet for this article.
2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28431015/large-scale-collection-of-full-length-cdna-and-transcriptome-analysis-in-hevea-brasiliensis
#17
Yuko Makita, Kiaw Kiaw Ng, G Veera Singham, Mika Kawashima, Hideki Hirakawa, Shusei Sato, Ahmad Sofiman Othman, Minami Matsui
Natural rubber has unique physical properties that cannot be replaced by products from other latex-producing plants or petrochemically produced synthetic rubbers. Rubber from Hevea brasiliensis is the main commercial source for this natural rubber that has a cis-polyisoprene configuration. For sustainable production of enough rubber to meet demand elucidation of the molecular mechanisms involved in the production of latex is vital. To this end, we firstly constructed rubber full-length cDNA libraries of RRIM 600 cultivar and sequenced around 20,000 clones by the Sanger method and over 15,000 contigs by Illumina sequencer...
April 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28427280/progress-in-terpene-synthesis-strategies-through-engineering-of-saccharomyces-cerevisiae
#18
Kalaivani Paramasivan, Sarma Mutturi
Terpenes are natural products with a remarkable diversity in their chemical structures and they hold a significant market share commercially owing to their distinct applications. These potential molecules are usually derived from terrestrial plants, marine and microbial sources. In vitro production of terpenes using plant tissue culture and plant metabolic engineering, although receiving some success, the complexity in downstream processing because of the interference of phenolics and product commercialization due to regulations that are significant concerns...
April 20, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28419968/current-insights-into-pathogenesis-of-parkinson-s-disease-approach-to-mevalonate-pathway-and-protective-role-of-statins
#19
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Katayoun Khoshbin, Ahmad Reza Dehpour
Although Parkinson's disease (PD) is considered as the second most common life threatening age-related neurodegenerative disorder, but the underlying mechanisms for pathogenesis of PD are remained to be fully found. However, a complex relationship between genetic and environmental predisposing factors are involved in progression of PD. Dopaminergic neuronal cell death caused by mutations and accumulation of α-synuclein in Lewy bodies and neurites was suggested as the main strategy for PD, but current studies have paid attention to the role of mevalonate pathway in incidence of neurodegenerative diseases including PD...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28419419/the-isoprenoid-derivative-n6-benzyladenosine-cm223-exerts-antitumor-effect-in-glioma-patient-derived-primary-cells-through-the-mevalonate-pathway
#20
Elena Ciaglia, Manuela Grimaldi, Mario Abate, Mario Scrima, Manuela Rodriquez, Chiara Laezza, Roberta Ranieri, Simona Pisanti, Pierangela Ciuffreda, Clementina Manera, Patrizia Gazzerro, Anna Maria D'Ursi, Maurizio Bifulco
BACKGROUND AND PURPOSE: N6-Isopentenyladenosine (i6A) is a modified nucleoside exerting in vitro and in vivo antiproliferative effects. We previously demonstrated that the i6A action is correlated to farnesyl pyrophosphate synthase (FPPS) expression and activity, a key enzyme involved in the mevalonate (MVA) pathway, which is found aberrant in brain cancer. To develop new anti-glioma strategies, we looked for other valuable compounds exhibiting improved activity as compared to i6A. EXPERIMENTAL APPROACH: we designed and synthesized i6A derivatives characterized by the introduction of diverse chemical moieties in the N6 position of adenosine and tested for their efficacy in U87 and primary derived patient's glioma cell model...
April 18, 2017: British Journal of Pharmacology
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