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https://www.readbyqxmd.com/read/29674683/amino-acid-signature-in-human-melanoma-cell-lines-from-different-disease-stages
#1
Christine Wasinger, Alexandra Hofer, Oliver Spadiut, Martin Hohenegger
Cancer cells rewire metabolism to sustain high proliferation rates. Beside glycolysis and glutaminolysis, amino acids substitute as energy source, feed fatty acid biosynthesis and represent part of the secretome of transformed cells, including melanoma. We have therefore investigated acetate, pyruvate and the amino acid composition of the secretome of human melanoma cells representing the early slow (WM35, WM278, WM793b and VM21) and metastatic fast (A375, 518a2, 6F and WM8) growth phase in order to identify possible signalling components within these profiles...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29672609/heterologous-expression-of-2-methylisoborneol-2-methylenebornane-biosynthesis-genes-in-escherichia-coli-yields-novel-c11-terpenes
#2
Max J Kschowak, Hannah Wortmann, Jeroen S Dickschat, Jens Schrader, Markus Buchhaupt
The structural diversity of terpenoids is limited by the isoprene rule which states that all primary terpene synthase products derive from methyl-branched building blocks with five carbon atoms. With this study we discover a broad spectrum of novel terpenoids with eleven carbon atoms as byproducts of bacterial 2-methylisoborneol or 2-methylenebornane synthases. Both enzymes use 2-methyl-GPP as substrate, which is synthesized from GPP by the action of a methyltransferase. We used E. coli strains that heterologously produce different C11-terpene synthases together with the GPP methyltransferase and the mevalonate pathway enzymes...
2018: PloS One
https://www.readbyqxmd.com/read/29670091/inhibition-of-the-mevalonate-pathway-enhances-cancer-cell-oncolysis-mediated-by-m1-virus
#3
Jiankai Liang, Li Guo, Kai Li, Xiao Xiao, Wenbo Zhu, Xiaoke Zheng, Jun Hu, Haipeng Zhang, Jing Cai, Yaya Yu, Yaqian Tan, Chuntao Li, Xincheng Liu, Cheng Hu, Ying Liu, Pengxin Qiu, Xingwen Su, Songmin He, Yuan Lin, Guangmei Yan
Oncolytic virus is an attractive anticancer agent that selectively lyses cancer through targeting cancer cells rather than normal cells. Although M1 virus is effective against several cancer types, certain cancer cells present low sensitivity to it. Here we identified that most of the components in the cholesterol biosynthesis pathway are downregulated after M1 virus infection. Further functional studies illustrate that mevalonate/protein farnesylation/ras homolog family member Q (RHOQ) axis inhibits M1 virus replication...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29627155/alendronate-and-fti-277-combination-as-a-possible-therapeutic-approach-for-hepatocellular-carcinoma-an-in-vitro-study
#4
Amber Ilyas, Zehra Hashim, Iffat Saeed Channa, Shamshad Zarina
BACKGROUND: An important product of mevalonate pathway is downstream synthesis of isoprenoid units that has long been implicated in development and progression of tumor. It has been speculated that inhibition of protein prenylation might be therapeutically beneficial. The objective of current study was to evaluate antitumor potential of a novel therapeutic combination of mevalonate pathway inhibitors, FTI-277 and alendronate. We also examined differentially expressed proteins in response to treatment using proteomics approach...
March 24, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/29626418/bergamot-natural-products-eradicate-cancer-stem-cells-cscs-by-targeting-mevalonate-rho-gdi-signalling-and-mitochondrial-metabolism
#5
Marco Fiorillo, Maria Peiris-Pagès, Rosa Sanchez-Alvarez, Lucia Bartella, Leonardo Di Donna, Vincenza Dolce, Giovanni Sindona, Federica Sotgia, Anna Rita Cappello, Michael P Lisanti
Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed "BMF", has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-CoA-reductase). Moreover, our results indicate that BMF functionally inhibits several key characteristics of CSCs. More specifically, BMF effectively i) reduced ALDH activity, ii) blocked mammosphere formation and iii) inhibited the activation of CSC-associated signalling pathways (STAT1/3, Notch and Wnt/beta-catenin) targeting Rho-GDI-signalling...
April 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29625976/identification-of-a-sesquiterpene-synthase-3-hydroxy-3-methylglutaryl-coa-synthase-fusion-protein-responsible-for-hirsutene-biosynthesis-in-stereum-hirsutum
#6
Christopher M Flynn, Claudia Schmidt-Dannert
The wood-rotting mushroom Stereum hirsutum is a known producer of a large number of namesake hirsutenoids, many with important bioactivities. Hirsutenoids form structurally diverse and distinct class of sesquiterpenoids. No genes involved in hirsutenoid biosynthesis have yet been identified, or their enzymes characterized. Here we describe the cloning and functional characterization of a hirsutene synthase as an unexpected fusion protein of a sesquiterpene synthase (STSs) with a C-terminal 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) domain...
April 6, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29615539/induction-regulation-and-roles-of-neural-adhesion-molecule-l1cam-in-cellular-senescence
#7
Blanka Mrazkova, Rastislav Dzijak, Terezie Imrichova, Lenka Kyjacova, Peter Barath, Petr Dzubak, Dusan Holub, Marian Hajduch, Zuzana Nahacka, Ladislav Andera, Petr Holicek, Pavla Vasicova, Olena Sapega, Jiri Bartek, Zdenek Hodny
Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new cell-surface proteins differentially expressed on human SC. Besides previously reported proteins enriched on SC, we identified 78 proteins enriched and 73 proteins underrepresented in replicatively senescent BJ fibroblasts, including L1CAM, whose expression is normally restricted to the neural system and kidneys...
March 28, 2018: Aging
https://www.readbyqxmd.com/read/29600537/hyper-immunoglobulin-d-syndrome-with-novel-mutations-in-an-afebrile-infant
#8
Simi D Cadmus, Reid Green, Ruy Carrasco, Moise L Levy, Lucia Z Diaz
Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory syndrome in which a mevalonate kinase deficiency results due to mutations of the mevalonate kinase gene. We report a case of an Asian male infant who was found to have hyper-immunoglobulin D syndrome in the absence of fever. His skin manifestations included cephalic pustulosis as well recurrent transient and fixed pink plaques and nodules on the face and extremities. Subsequent examination revealed hyper-immunoglobulin D syndrome with two novel allelic mutations in the mevalonate kinase gene: c...
March 30, 2018: Pediatric Dermatology
https://www.readbyqxmd.com/read/29599115/the-upr-mt-protects-caenorhabditis-elegans-from-mitochondrial-dysfunction-by-upregulating-specific-enzymes-of-the-mevalonate-pathway
#9
Olga Oks, Shany Lewin, Irina Langier Goncalves, Amir Sapir
The mevalonate pathway is the primary target of the cholesterol-lowering drugs statins, some of the most widely prescribed medicines of all time. The pathway's enzymes not only catalyze the synthesis of cholesterol but also of diverse metabolites such as mitochondrial electron carriers and isoprenyls. Recently, it has been shown that one type of mitochondrial stress response, the UPRmt , can protect yeast, C. elegans, and cultured human cells from the deleterious effects of mevalonate pathway inhibition by statins...
March 29, 2018: Genetics
https://www.readbyqxmd.com/read/29593117/genetic-defects-in-sapk-signalling-chromatin-regulation-vesicle-transport-and-coa-related-lipid-metabolism-are-rescued-by-rapamycin-in-fission-yeast
#10
Kenichi Sajiki, Yuria Tahara, Alejandro Villar-Briones, Tomáš Pluskal, Takayuki Teruya, Ayaka Mori, Mitsuko Hatanaka, Masahiro Ebe, Takahiro Nakamura, Keita Aoki, Yukinobu Nakaseko, Mitsuhiro Yanagida
Rapamycin inhibits TOR (target of rapamycin) kinase, and is being used clinically to treat various diseases ranging from cancers to fibrodysplasia ossificans progressiva. To understand rapamycin mechanisms of action more comprehensively, 1014 temperature-sensitive (ts) fission yeast ( Schizosaccharomyces pombe ) mutants were screened in order to isolate strains in which the ts phenotype was rescued by rapamycin. Rapamycin-rescued 45 strains, among which 12 genes responsible for temperature sensitivity were identified...
March 2018: Open Biology
https://www.readbyqxmd.com/read/29575963/innovations-in-asthma-therapy-is-there-a-role-for-inhaled-statins
#11
Amir A Zeki, Mona Elbadawi-Sidhu
Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings...
March 26, 2018: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/29574631/oxidative-stress-as-a-possible-mechanism-of-statin-induced-myopathy
#12
REVIEW
Yasin Ahmadi, Amir Ghorbanihaghjo, Mohsen Naghi-Zadeh, Neda Lotfi Yagin
Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS)...
March 24, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29573412/improved-squalene-production-through-increasing-lipid-contents-in-saccharomyces-cerevisiae
#13
Liu-Jing Wei, Suryang Kwak, Jing-Jing Liu, Stephan Lane, Qiang Hua, Dae-Hyuk Kweon, Yong-Su Jin
Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for pharmacology, flavor, and biofuel industries. Microbial production of squalene has been of great interest due to its limited availability, and increasing prices extracted from animal and plant tissues. Here we report genetic perturbations that synergistically improve squalene production in Saccharomyces cerevisiae. As reported previously, overexpression of a truncated HMG-CoA reductase 1 (tHMG1) led to the accumulation 20-fold higher squalene than a parental strain...
March 24, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29568741/alteration-of-mevalonate-pathway-in-rat-splenic-lymphocytes-possible-role-in-cytokines-secretion-regulated-by-l-theanine
#14
Chengjian Li, Qiongxian Yan, Shaoxun Tang, Wenjun Xiao, Zhiliang Tan
L-Theanine is a nonprotein amino acid in tea, and its immunomodulatory function has been confirmed. This study aimed to investigate the effect of L-theanine addition on cytokines secretion in rat splenic lymphocytes and explore its potential immunomodulatory effects on the mevalonate biosynthetic pathway. Our results showed that L-theanine treatment did not influence the proliferation and division indexes of the splenic lymphocytes subsets. Interestingly, L-theanine treatment had regulated the contents of IFN- γ , IL-2, IL-4, IL-10, IL-12, and TNF- α   ( P < 0...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29567200/the-mek5-erk5-mitogen-activated-protein-kinase-cascade-is-an-effector-pathway-of-bone-sustaining-bisphosphonates-that-regulates-osteogenic-differentiation-and-mineralization
#15
Christian Adam, Lucia Glück, Regina Ebert, Matthias Goebeler, Franz Jakob, Marc Schmidt
Bisphosphonates play an important role in the treatment of metabolic bone diseases such as osteoporosis. In addition to their anti-resorptive activity by triggering osteoclast apoptosis, nitrogen-containing bisphosphonates (N-BP) may also influence osteogenic differentiation, which might rely on their capacity to inhibit the mevalonate pathway. In vascular endothelial cells inhibition of this pathway by cholesterol-lowering statins activates the MEK5/ERK5 mitogen-activated protein kinase cascade, which plays an important role in cellular differentiation, apoptosis or inflammatory processes...
March 19, 2018: Bone
https://www.readbyqxmd.com/read/29562920/the-safety-of-live-attenuated-vaccines-in-patients-using-il-1-or-il-6-blockade-an-international-survey
#16
Jerold Jeyaratnam, Nienke M Ter Haar, Helen J Lachmann, Ozgur Kasapcopur, Amanda K Ombrello, Donato Rigante, Fatma Dedeoglu, Ezgi H Baris, Sebastiaan J Vastert, Nico M Wulffraat, Joost Frenkel
BACKGROUND: Withholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade. METHODS: We contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases...
March 21, 2018: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/29552677/mechanistic-studies-of-1-deoxy-d-xylulose-5-phosphate-synthase-from-deinococcus-radiodurans
#17
Sumit Handa, Daniel R Dempsey, Divya Ramamoorthy, Nanci Cook, Wayne C Guida, Tyler J Spradling, Justin K White, H Lee Woodcock, David J Merkler
The non-mevalonate dependent (NMVA) pathway for the biosynthesis of isopentenyl pyrophosphate and dimethylallyl pyrophosphate is the sole source of these terpenoids for the production of isoprenoids in the apicomplexan parasites, in many eubacteria, and in plants. The absence of this pathway in higher organisms has opened a new platform for the development of novel antibiotics and anti-malarials. The enzyme catalyzing the first step of the NMVA pathway is 1-deoxy-D-xylulose-5-phosphate synthase (DXPS). DXPS catalyzes the thiamine pyrophosphate- and Mg (II)-dependent conjugation of pyruvate and D-glyceraldehyde-3-phosphate to form 1-deoxy-D-xylulose-5-phosphate and CO2 ...
2018: Biochemistry & Molecular Biology Journal
https://www.readbyqxmd.com/read/29550587/structural-modeling-identifies-plasmodium-vivax-4-diphosphocytidyl-2c-methyl-d-erythritol-kinase-ispe-as-a-plausible-new-antimalarial-drug-target
#18
Kavita Kadian, Sonam Vijay, Yash Gupta, Ritu Rawal, Jagbir Singh, Anup Anvikar, Veena Pande, Arun Sharma
Malaria parasites utilize Methylerythritol phosphate (MEP) pathway for synthesis of isoprenoid precursors which are essential for maturation and survival of parasites during erythrocytic and gametocytic stages. The absence of MEP pathway in the human host establishes MEP pathway enzymes as a repertoire of essential drug targets. The fourth enzyme, 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) has been proved essential in pathogenic bacteria, however; it has not yet been studied in any Plasmodium species...
March 14, 2018: Parasitology International
https://www.readbyqxmd.com/read/29549002/development-of-a-plasmid-based-tunable-tolc-derived-expression-system-for-application-in-cupriavidus-necator-h16
#19
Elhussiny A Aboulnaga, Huibin Zou, Thorsten Selmer, Mo Xian
Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism...
March 13, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29535738/valproic-acid-combined-with-zoledronate-enhance-%C3%AE-%C3%AE-t-cell-mediated-cytotoxicity-against-osteosarcoma-cells-via-the-accumulation-of-mevalonate-pathway-intermediates
#20
Shengdong Wang, Hengyuan Li, Chenyi Ye, Peng Lin, Binghao Li, Wei Zhang, Lingling Sun, Zhan Wang, Deting Xue, Wangsiyuan Teng, Xingzhi Zhou, Nong Lin, Zhaoming Ye
The long-term survival of osteosarcoma has remained unchanged in the last several decades. Immunotherapy is proved to be a promising therapeutic strategy against osteosarcoma, especially for those with metastasis. Our previous study explored the sensibilization of zoledronate (ZOL) in γδ T cell-mediated cytotoxicity against osteosarcoma, but we have not yet elucidated the specific mechanism. Besides, high concentration is required to achieve these effects, whereas plasma ZOL concentration declines rapidly in the circulation...
2018: Frontiers in Immunology
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