keyword
MENU ▼
Read by QxMD icon Read
search

mevalonate

keyword
https://www.readbyqxmd.com/read/28303595/a-single-intra-articular-injection-of-fluvastatin-plga-microspheres-reduces-cartilage-degradation-in-rabbits-with-experimental-osteoarthritis
#1
Norio Goto, Ken Okazaki, Yukio Akasaki, Kohei Ishihara, Koji Murakami, Kiyoshi Koyano, Yasunori Ayukawa, Noriyuki Yasunami, Tomohiro Masuzaki, Yasuharu Nakashima
Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes...
March 17, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28302121/type-iis-restriction-based-combinatory-modulation-technique-for-metabolic-pathway-optimization
#2
Lijun Ye, Ping He, Qingyan Li, Xueli Zhang, Changhao Bi
BACKGROUND: One of the most important research subjects of metabolic engineering is pursuing a balanced metabolic pathway, which is the basis of an efficient cell factory. In this work, we dedicated to develop a simple and efficient technique to modulate expression of multiple genes simultaneously, and select for the optimal regulation pattern. RESULTS: A Type IIs restriction based combinatory modulation (TRCM) technique was designed and established in the research...
March 16, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28300835/geranylgeranyl-diphosphate-synthase-inhibition-induces-apoptosis-that-is-dependent-upon-ggpp-depletion-erk-phosphorylation-and-caspase-activation
#3
Sherry S Agabiti, Jin Li, Andrew J Wiemer
Bisphosphonates are diphosphate analogs that inhibit the intermediate enzymes of the mevalonate pathway. Here, we compared the effects of a farnesyl diphosphate synthase inhibitor, zoledronate, and a geranylgeranyl diphosphate synthase (GGDPS) inhibitor, digeranyl bisphosphonate (DGBP), on lymphocytic leukemia cell proliferation and apoptosis. Both zoledronate and DGBP inhibited proliferation with DGBP doing so more potently. DGBP was markedly less toxic than zoledronate toward the viability of healthy human peripheral blood mononuclear cells...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28298072/the-anti-osteoporotic-and-anti-atherogenic-effects-of-alendronate-and-simvastatin-in-ovariectomized-rats-fed-high-fat-diet-a-comparative-study-of-combination-therapy-versus-monotherapy
#4
Maha Tarek Mohamed, Sally A Abuelezz, Suzi Sobhy Atalla, Lobna Fouad Abd El Aziz, Sonia Salib Gorge
AIM: Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD). MAIN METHODS: 60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d)...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28285413/comprehensive-assessment-of-the-genes-involved-in-withanolide-biosynthesis-from-withania-somnifera-chemotype-specific-and-elicitor-responsive-expression
#5
Aditya Vikram Agarwal, Parul Gupta, Deeksha Singh, Yogeshwar Vikram Dhar, Deepak Chandra, Prabodh Kumar Trivedi
Withania somnifera (L.) Dunal (Family, Solanaceae), is among the most valuable medicinal plants used in Ayurveda owing to its rich reservoir of pharmaceutically active secondary metabolites known as withanolides. Withanolides are C28-steroidal lactones having a triterpenoidal metabolic origin synthesised via mevalonate (MVA) pathway and methyl-D-erythritol-4-phosphate (MEP) pathway involving metabolic intermediacy of 24-methylene (C30-terpenoid) cholesterol. Phytochemical studies suggest differences in the content and/or nature of withanolides in different tissues of different chemotypes...
March 11, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28284974/mevalonolactone-disrupts-mitochondrial-functions-and-induces-permeability-transition-pore-opening-in-rat-brain-mitochondria-implications-for-the-pathogenesis-of-mevalonic-aciduria
#6
Cristiane Cecatto, Alexandre Umpierrez Amaral, Janaína Camacho da Silva, Alessandro Wajner, Kálita Dos Santos Godoy, Rafael Teixeira Ribeiro, Aline de Mello Gonçalves, Carmen Regla Vargas, Moacir Wajner
Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca(2+) in the brain, besides inducing mitochondrial swelling...
March 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28276528/variability-in-statin-induced-changes-in-gene-expression-profiles-of-pancreatic-cancer
#7
Helena Gbelcová, Silvie Rimpelová, Tomáš Ruml, Marie Fenclová, Vítek Kosek, Jana Hajšlová, Hynek Strnad, Michal Kolář, Libor Vítek
Statins, besides being powerful cholesterol-lowering drugs, also exert potent anti-proliferative activities. However, their anti-cancer efficacy differs among the individual statins. Thus, the aim of this study was to identify the biological pathways affected by individual statins in an in vitro model of human pancreatic cancer. The study was performed on a human pancreatic cancer cell line MiaPaCa-2, exposed to all commercially available statins (12 μM, 24 h exposure). DNA microarray analysis was used to determine changes in the gene expression of treated cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230855/simvastatin-induced-cell-cycle-arrest-through-inhibition-of-stat3-skp2-axis-and-activation-of-ampk-to-promote-p27-and-p21-accumulation-in-hepatocellular-carcinoma-cells
#8
Sin-Ting Wang, Hsiu J Ho, Jaw-Town Lin, Jeng-Jer Shieh, Chun-Ying Wu
Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and is one of the leading causes of cancer-related death worldwide. Simvastatin, an HMG-CoA reductase inhibitor, which decreases cholesterol synthesis by inhibiting mevalonate pathways and is widely used to treat cardiovascular diseases. Simvastatin exhibits anticancer effects against several malignancies. However, the molecular mechanisms underlying the anticancer effects of simvastatin on HCC are still not well understood. In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28217906/production-of-taxadiene-by-engineering-of-mevalonate-pathway-in-escherichia-coli-and-endophytic-fungus-alternaria-alternata-tpf6
#9
Guangkai Bian, Yujie Yuan, Hui Tao, Xiaofei Shi, Xiaofang Zhong, Yichao Han, Shuai Fu, Chengxiang Fang, Zixin Deng, Tiangang Liu
Taxol (paclitaxel) is a diterpenoid compound with significant and extensive applications in the treatment of cancer. The production of Taxol and relevant intermediates by engineered microbes is an attractive alternative to the semichemical synthesis of Taxol. In this study, based on a previously developed platform, we first established taxadiene production in mutant E. coli T2 and T4 by engineering of the mevalonate (MVA) pathway. We then developed an Agrobacterium tumefaciens-mediated transformation (ATMT) method and verified the strength of heterologous promoters in Alternaria alternata TPF6...
February 20, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28212283/the-effects-of-tocotrienol-and-lovastatin-co-supplementation-on-bone-dynamic-histomorphometry-and-bone-morphogenetic-protein-2-expression-in-rats-with-estrogen-deficiency
#10
Kok-Yong Chin, Saif Abdul-Majeed, Norazlina Mohamed, Soelaiman Ima-Nirwana
Both tocotrienol and statins are suppressors of the mevalonate pathway. Supplementation of tocotrienol among statin users could potentially protect them against osteoporosis. This study aimed to compare the effects of tocotrienol and lovastatin co-supplementation with individual treatments on bone dynamic histomorphometric indices and bone morphogenetic protein-2 (BMP-2) gene expression in ovariectomized rats. Forty-eight female Sprague-Dawley rats were randomized equally into six groups. The baseline was sacrificed upon receipt...
February 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28209347/high-resolution-mass-spectrometry-based-method-applicable-for-a-wide-range-of-3-hydroxy-3-methyl-glutaryl-coenzyme-a-reductase-inhibitors-in-blood-serum-including-intermediates-and-products-of-the-cholesterol-biosynthetic-pathway
#11
Vít Kosek, Milena Stránská, Marie Fenclová, Tomáš Ruml, Libor Vítek, Jana Hajšlová
Statins belong to the major class of hypolipidemic drugs. They act as competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway. This inhibition not only leads to the depletion of cholesterol and its fatty acid esters, but also to the depletion of the intermediates of this metabolic pathway (mainly pyrophosphates), which can play an important role in tumor proliferation. The aim of the current study was to establish a versatile multi-analyte method capable of quantitative determination of various currently-used statins, together with free cholesterol (FC), cholesterol esters (CEs), and some key intermediates of the mevalonate pathway occurring in human serum...
March 17, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28208018/pharmacophore-mapping-of-thienopyrimidine-based-monophosphonate-thp-mp-inhibitors-of-the-human-farnesyl-pyrophosphate-synthase
#12
Jaeok Park, Chun Yuen Leung, Alexios N Matralis, Cyrus M Lacbay, Michail Tsakos, Guillermo Fernandez De Troconiz, Albert M Berghuis, Youla S Tsantrizos
The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases...
February 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28196976/biosynthetic-studies-on-terpenoids-produced-by-streptomyces
#13
REVIEW
Tomohisa Kuzuyama
Terpenoids are a large and highly diverse group of natural products. All terpenoids are biosynthesized from isoprenyl diphosphate formed by the consecutive condensation of the five-carbon monomer isopentenyl diphosphate (IPP) to its isomer dimethylallyl diphosphate (DMAPP). Two distinct biosynthetic pathways produce the essential primary metabolites IPP and DMAPP: the 2-C-methylerythritol 4-phosphate pathway and the mevalonate pathway. The isoprenyl substrates can be cyclized by terpene cyclase into single-ring or multi-ring products, which can be further diversified by subsequent modification reactions, such as hydroxylation and glycosylation...
February 15, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28188954/comparative-glandular-trichome-transcriptome-based-gene-characterization-reveals-reasons-for-differential-menthol-biosynthesis-in-mentha-species
#14
Md Qussen Akhtar, Nida Qamar, Pallavi Yadav, Pallavi Kulkarni, Ajay Kumar, Ajit Kumar Shasany
The genes involved in menthol biosynthesis are reported earlier in Mentha × piperita. But the information on these genes is not available in Mentha arvensis. To bridge the gap in knowledge on differential biosynthesis of monoterpenes leading to compositional variation in the essential oil of these species, a comparative transcriptome analysis of the glandular trichome was carried out. In addition to the MVA and MEP pathway genes, about 210 and 196 different terpene synthases (TPS) transcripts were identified from annotation in M...
February 11, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28188410/simvastatin-inhibits-il-1%C3%AE-induced-apoptosis-and-extracellular-matrix-degradation-by-suppressing-the-nf-kb-and-mapk-pathways-in-nucleus-pulposus-cells
#15
Ji Tu, Wentian Li, Yukun Zhang, Xinghuo Wu, Yu Song, Liang Kang, Wei Liu, Kun Wang, Shuai Li, Wenbin Hua, Cao Yang
Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway. Some studies have shown that statins may have the potential to inhibit intervertebral disk (IVD) degeneration (IDD). Interleukin (IL)-1β, a catabolic cytokine, is a key regulator of IDD. This study aimed to investigate the mechanism underlying the effect of simvastatin on IDD. The viability of nucleus pulposus (NP) cells was determined by the methyl-thiazolyl-tetrazolium (MTT) assay. The apoptosis of NP cells was measured by flow cytometric analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blotting of relevant apoptotic proteins...
February 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28185100/effects-of-acetoacetyl-coa-synthase-expression-on-production-of-farnesene-in-saccharomyces-cerevisiae
#16
Stefan Tippmann, Raphael Ferreira, Verena Siewers, Jens Nielsen, Yun Chen
Efficient production of sesquiterpenes in Saccharomyces cerevisiae requires a high flux through the mevalonate pathway. To achieve this, the supply of acetyl-CoA plays a crucial role, partially because nine moles of acetyl-CoA are necessary to produce one mole of farnesyl diphosphate, but also to overcome the thermodynamic constraint imposed on the first reaction, in which acetoacetyl-CoA is produced from two moles of acetyl-CoA by acetoacetyl-CoA thiolase. Recently, a novel acetoacetyl-CoA synthase (nphT7) has been identified from Streptomyces sp...
February 9, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28181143/the-complex-interplay-among-hepatocytes-and-immune-cells-at-the-crossroad-between-inflammation-and-cholesterol-metabolism-in-hyperglycemia
#17
Maurizio Bifulco, Simona Pisanti, Elena Ciaglia
An intriguing piece of evidence for the inflammatory story of type 2 diabetes has come to the light. A recent study by Okin and colleagues adds new clues to the interplay between cholesterol metabolism and immunity and how it impacts glucose homeostasis in inflammatory conditions. But some questions are a still unsolved conundrum. Here we suggest to better dissect the regulatory mechanism of Mevalonate pathway and to underpin a new causative link between immunometabolic dysregulation and diabetes.
February 8, 2017: Endocrine
https://www.readbyqxmd.com/read/28178435/an-up-to-date-approach-to-a-patient-with-a-suspected-autoinflammatory-disease
#18
REVIEW
Merav Lidar, Eitan Giat
Autoinflammatory diseases (AID) are characterized by seemingly unprovoked self-limited attacks of fever and systemic inflammation potentially leading to amyloidosis. Familial Mediterranean fever (FMF) is the most common AID and therefore the most studied. Besides FMF, the other main hereditary AID are tumor necrosis factor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic fever syndrome (CAPS). These hereditary diseases result from a mutant gene that is involved in the regulation of inflammation, resulting in a characteristic clinical phenotype...
January 30, 2017: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/28157221/microbial-modulation-of-bacoside-a-biosynthetic-pathway-and-systemic-defense-mechanism-in-bacopa-monnieri-under-meloidogyne-incognita-stress
#19
Rupali Gupta, Akanksha Singh, Madhumita Srivastava, Vivek Singh, M M Gupta, Rakesh Pandey
Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138930/recombinant-3-hydroxy-3-methyl-glutaryl-coa-reductase-from-candida-glabrata-rec-cghmgr-obtained-by-heterologous-expression-as-a-novel-therapeutic-target-model-for-testing-synthetic-drugs
#20
Dulce Andrade-Pavón, Roberto I Cuevas-Hernández, José G Trujillo-Ferrara, César Hernández-Rodríguez, J Antonio Ibarra, Lourdes Villa-Tanaca
The enzyme 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGR) is a glycoprotein of the endoplasmic reticulum that participates in the mevalonate pathway, the precursor of cholesterol in human and ergosterol in fungi. This enzyme has three domains: transmembrane, binding, and soluble. In this study, we expressed and purified the soluble fraction of the HMGR enzyme from Candida glabrata (CgHMGR) in an Escherichia coli heterologous system and used it as a model for studying its inhibitory activity. The soluble fraction of CgHMGR was fused to the maltose binding protein (MBP), purified, and characterized...
January 30, 2017: Applied Biochemistry and Biotechnology
keyword
keyword
44301
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"