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https://www.readbyqxmd.com/read/29345110/remarkable-similarity-in-plasmodium-falciparum-and-plasmodium-vivax-geranylgeranyl-diphosphate-synthase-ggpps-dynamics-and-its-implication-for-anti-malarial-drug-design
#1
Aishwarya Venkatramani, Clarisse G Ricci, Eric Oldfield, J Andrew McCammon
Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a growing cause of morbidity and mortality. P. falciparum is more lethal than is P. vivax, but there is a vital need for effective drugs against both species. Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the biosynthesis of quinones and in protein prenylation, and has been proposed to be a malaria drug target. However, the structure of P. falciparum GGPPS (PfGGPPS) has not been determined, due to difficulties in crystallization...
January 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29319354/inhibition-of-the-rhoa-rho-associated-coiled-coil-containing-protein-kinase-1-pathway-is-involved-in-the-therapeutic-effects-of-simvastatin-on-pulmonary-arterial-hypertension
#2
Wei-Hua Liu, Xiao-Hong Xu, Qin Luo, Hong-Liang Zhang, Yong Wang, Qun-Ying Xi, Zhi-Hui Zhao, Zhi-Hong Liu
BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i...
January 10, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29298513/andrographolide-inhibits-oxidized-ldl-induced-cholesterol-accumulation-and-foam-cell-formation-in-macrophages
#3
Hung-Chih Lin, Chong-Kuei Lii, Hui-Chun Chen, Ai-Hsuan Lin, Ya-Chen Yang, Haw-Wen Chen
oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29236027/simvastatin-inhibits-cell-proliferation-and-migration-in-human-anaplastic-thyroid-cancer
#4
Mei-Chieh Chen, Yuan-Chin Tsai, Jen-Ho Tseng, Jr-Jiun Liou, Steve Horng, Heng-Ching Wen, Yu-Ching Fan, Wen-Bin Zhong, Sung-Po Hsu
Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 μM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29229608/statin-induced-cancer-cell-death-can-be-mechanistically-uncoupled-from-prenylation-of-ras-family-proteins
#5
Rosemary Yu, Joseph Longo, Jenna E van Leeuwen, Peter J Mullen, Wail Ba-Alawi, Benjamin Haibe-Kains, Linda Z Penn
The statin family of drugs preferentially trigger tumor cell apoptosis by depleting mevalonate pathway metabolites farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including the oncoproteins of the RAS superfamily. However, accumulating data indicate that activation of the RAS superfamily are poor biomarkers of statin sensitivity, and the mechanism of statin-induced tumor-specific apoptosis remains unclear. Here we demonstrate that cancer cell death triggered by statins can be uncoupled from prenylation of the RAS superfamily of oncoproteins...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29179489/saikosaponin-a-inhibits-il-1%C3%AE-induced-inflammatory-mediators-in-human-osteoarthritis-chondrocytes-by-activating-lxr%C3%AE
#6
Hang Gao, Yanyan Song, Dongsong Li, Wei Feng, Jianguo Liu
Saikosaponin a (SSa), one of the main active components of Bupleurum falcatum, has been reported to have anti-inflammatory effect. In the present study, we investigated the anti-inflammatory effect of SSa on IL-1β-stimulated human osteoarthritis chondrocytes. The cells were pretreated with SSa 12 h before IL-1β treatment. The production of PGE2 and NO were detected by ELISA and Griess method. The levels of MMP1, MMP3, and MMP13 were measured by ELISA and qRT-PCR. The expression of NF-κB and LXRα were tested by western blot analysis...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29167270/ubia-prenyltransferase-domain-containing-protein-1-modulates-hmg-coa-reductase-degradation-to-coordinate-synthesis-of-sterol-and-nonsterol-isoprenoids
#7
Marc M Schumacher, Dong-Jae Jun, Brittany M Johnson, Russell A DeBose-Boyd
UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2. We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG CoA reductase. UBIAD1 binding inhibits sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several mechanisms for feedback control of this rate-limiting enzyme in the branched pathway that produces cholesterol and nonsterol isoprenoids such as GGpp. Accumulation of GGpp in ER membranes triggers release of UBIAD1 from reductase, permitting its maximal ERAD and ER-to-Golgi transport of UBIAD1...
November 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29166855/identification-of-differentially-expressed-genes-in-flower-leaf-and-bulb-scale-of-lilium-oriental-hybrid-sorbonne-and-putative-control-network-for-scent-genes
#8
Fang Du, Junmiao Fan, Ting Wang, Yun Wu, Donald Grierson, Zhongshan Gao, Yiping Xia
BACKGROUND: Lily is an economically important plant, with leaves and bulbs consisting of overlapping scales, large ornamental flowers and a very large genome. Although it is recognized that flowers and bulb scales are modified leaves, very little is known about the genetic control and biochemical differentiation underlying lily organogenesis and development. Here we examined the differentially expressed genes in flower, leaf and scale of lily, using RNA-sequencing, and identified organ-specific genes, including transcription factors, genes involved in photosynthesis in leaves, carbohydrate metabolism in bulb scales and scent and color production in flowers...
November 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29142397/chemical-composition-antimicrobial-and-antitumor-potentiality-of-essential-oil-of-ferula-tingitana-l-apiaceae-grow-in-libya
#9
Waleed Elghwaji, Abeer Mohamed El-Sayed, Kadriya S El-Deeb, Aly M ElSayed
Background: Ferula tingitana L. (Apiaceae) has been considered to have abortive and menstruation-inducing properties. It used to treat sore throat, fever, indigestion, and pains. Objectives: The objective of this study is to establish the chemical composition of the essential oil of flower, leaves of F. tingitana, and to throw light on antimicrobial, cytotoxic activities of Libyan plant. Materials and Methods: The chemical composition of the essential oil of flower (0...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29081786/probing-the-single-key-amino-acid-responsible-for-the-novel-catalytic-function-of-ent-kaurene-oxidase-supported-by-nadph-cytochrome-p450-reductases-in-tripterygium-wilfordii
#10
Ping Su, Hongyu Guan, Yifeng Zhang, Xing Wang, Linhui Gao, Yujun Zhao, Tianyuan Hu, Jiawei Zhou, Baowei Ma, Lichan Tu, Yuru Tong, Luqi Huang, Wei Gao
Tripterygium wilfordii produces not only ent-kaurene, which is an intermediate of gibberellin (GA) biosynthesis in flowering plants, but also 16α-hydroxy-ent-kaurane, whose physiological role has not been characterized. The two compounds are biosynthesized from the universal diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate (GGPP) by diterpene synthases, which have been discovered and functionally characterized in T. wilfordii. Here, we described the functional characterization of four cytochrome P450 reductases (TwCPR) and one ent-kaurene oxidase (TwKO)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28918530/exogenous-and-endogenous-increase-in-fungal-ggpp-increased-fungal-taxol-production
#11
Sameh S M Soliman, Kareem A Mosa, Ali A El-Keblawy, Mohamed I Husseiny
Taxol is an anticancer identified in both endophytic fungus and its host plant. Plant Taxol is a diterpenoid with geranylgeranyl diphosphate (GGPP) mediates the biosynthesis of its terpenoid moiety. Previous report has suggested that fungal Taxol may require terpenoid pathway for its biosynthesis. Here in this study, feeding a Taxol-producing endophytic fungus (Paraconiothyrium SSM001) with terpenoid precursors including isopentenyl pyrophosphate (IPP, isoprene) and GGPP enhanced Taxol production threefold and fivefold, respectively, compared to the control...
October 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28916945/simvastatin-enhances-radiation-sensitivity-of-colorectal-cancer-cells
#12
Georgios Karagkounis, Jennifer DeVecchio, Sylvain Ferrandon, Matthew F Kalady
INTRODUCTION: Neoadjuvant chemoradiation (CRT) for rectal cancer induces variable responses, and better response has been associated with improved oncologic outcomes. Our group has previously shown that the administration of HMG-CoA reductase inhibitors, commonly known as statins, is associated with improved response to neoadjuvant CRT in rectal cancer patients. The purpose of this study was to study the effects of simvastatin on colorectal cancer cells and explore its potential as a radiation-sensitizer in vitro...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28813599/tetraterpene-synthase-substrate-and-product-specificity-in-the-green-microalga-botryococcus-braunii-race-l
#13
Hem R Thapa, Su Tang, James C Sacchettini, Timothy P Devarenne
Recently, the biosynthetic pathway for lycopadiene, a C40 tetraterpenoid hydrocarbon, was deciphered from the L race of Botryococcus braunii, an alga that produces hydrocarbon oils capable of being converted into combustible fuels. The lycopadiene pathway is initiated by the squalene synthase (SS)-like enzyme lycopaoctaene synthase (LOS), which catalyzes the head-to-head condensation of two C20 geranylgeranyl diphosphate (GGPP) molecules to produce C40 lycopaoctaene. LOS shows unusual substrate promiscuity for SS or SS-like enzymes by utilizing C15 farnesyl diphosphate (FPP) and C20 phytyl diphosphate in addition to GGPP as substrates...
September 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28765914/atorvastatin-increases-fads1-fads2-and-elovl5-gene-expression-via-the-geranylgeranyl-pyrophosphate-dependent-rho-kinase-pathway-in-3t3-l1-cells
#14
Noriko Ishihara, Sawako Suzuki, Shou Tanaka, Yasuhiro Watanabe, Daiji Nagayama, Atsuhito Saiki, Tomoaki Tanaka, Ichiro Tatsuno
Numerous clinical studies have reported that statins increase the plasma concentration of arachidonic acid, which is an ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and decrease the concentrations of eicosapentaenoic acid and docosahexaenoic acid, which are ω‑3 LCPUFAs. These findings indicate that statins may affect the endogenous synthesis of LCPUFAs, which is regulated by fatty acid desaturases (FADSs) and elongation of very long‑chain fatty acids proteins (ELOVLs). The present study aimed to investigate the roles of the intrinsic mevalonate cascade and Rho‑dependent pathway in statin‑induced regulation of these desaturases and elongases, as well as cell viability using mouse 3T3‑L1 cells...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28736281/platycodin-d-suppressed-lps-induced-inflammatory-response-by-activating-lxr%C3%AE-in-lps-stimulated-primary-bovine-mammary-epithelial-cells
#15
Yanan Wang, Xu Zhang, Zhengkai Wei, Jingjing Wang, Yue Zhang, Mingyu Shi, Zhengtao Yang, Yunhe Fu
Platycodin D (PLD), a triterpenoid saponin derived from the root of Platycodon grandiflorum, has been reported to possess anti-inflammatory activity. However, the protective effect of PLD on mastitis has not been reported. In the present study, we aim to investigate the anti-inflammatory feature of PLD on the primary bovine mammary epithelial cells (bMEC) challenged with LPS. The cell viability of bMEC was measured by MTT assay. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the gene expression of pro-inflammatory cytokines and western blotting was carried out to measure the expression of LXRα and NF-κB...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28694802/the-response-regulator-slr1588-regulates-spsa-but-is-not-crucial-for-salt-acclimation-of-synechocystis-sp-pcc-6803
#16
Kuo Song, Martin Hagemann, Xiaoming Tan, Xuefeng Lu
Cyanobacterial sucrose biosynthesis is stimulated under salt stress, which could be used for biotechnological sugar production. It has been shown that the response regulator Slr1588 negatively regulates the spsA gene encoding sucrose-phosphate synthase and mutation of the slr1588 gene also affected the salt tolerance of Synechocystis (Chen et al., 2014). The latter finding is contrary to earlier observations (Hagemann et al., 1997b). Here, we observed that ectopic expression of slr1588 did not restore the salt tolerance of the slr1588 mutant, making the essential function of this response regulator for salt tolerance questionable...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28666798/insights-into-the-mevalonate-pathway-in-the-anticancer-effect-of-a-platinum-complex-on-human-gastric-cancer-cells
#17
Ling Qiu, Hui Yang, Gaochao Lv, Ke Li, Guiqing Liu, Wei Wang, Shanshan Wang, Xueyu Zhao, Minhao Xie, Jianguo Lin
A platinum(II) complex [Pt(en)]2ZL [en = ethylenediamine; ZL = 1-hydroxy-3(1H-imidazol-1-yl)ethane-1,1-diylbisphosphonic acid, commonly called as zoledronic acid] has been designed and synthesized recently in order to look for new anticancer drugs with high efficacy and low side effects. It exhibited cytotoxic effects on the human cancer cells SGC7901, HepG2, MCF-7, MDA-MB-231, HCT116, and U2OS, and the cytotoxicity against SGC7901 is particularly remarkable. It also showed higher cytotoxicity and better selectivity than the corresponding ligand ZL in inhibiting cancer cells SGC7901 and HepG2 rather than normal cells GES-1 and LO2...
September 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28655749/polyprenols-are-synthesized-by-a-plastidial-cis-prenyltransferase-and-influence-photosynthetic-performance
#18
Tariq A Akhtar, Przemysław Surowiecki, Hanna Siekierska, Magdalena Kania, Kristen Van Gelder, Kevin A Rea, Lilia K A Virta, Maritza Vatta, Katarzyna Gawarecka, Jacek Wojcik, Witold Danikiewicz, Daniel Buszewicz, Ewa Swiezewska, Liliana Surmacz
Plants accumulate a family of hydrophobic polymers known as polyprenols, yet how they are synthesized, where they reside in the cell, and what role they serve is largely unknown. Using Arabidopsis thaliana as a model, we present evidence for the involvement of a plastidial cis-prenyltransferase (AtCPT7) in polyprenol synthesis. Gene inactivation and RNAi-mediated knockdown of AtCPT7 eliminated leaf polyprenols, while its overexpression increased their content. Complementation tests in the polyprenol-deficient yeast ∆rer2 mutant and enzyme assays with recombinant AtCPT7 confirmed that the enzyme synthesizes polyprenols of ∼55 carbons in length using geranylgeranyl diphosphate (GGPP) and isopentenyl diphosphate as substrates...
July 2017: Plant Cell
https://www.readbyqxmd.com/read/28652177/inhibition-of-il-6-and-il-8-production-in-lps-stimulated-human-gingival-fibroblasts-by-glycyrrhizin-via-activating-lxr%C3%AE
#19
Na Zhang, Hui Lv, Bo-Hong Shi, Xin Hou, Xin Xu
The aim of this study was to clarify the anti-inflammatory effects and its molecular mechanism of glycyrrhizin on LPS-stimulated human gingival fibroblasts (HGFs), which will be of benefit for periodontitis treatment. An MTT assay was performed to assess the effects of glycyrrhizin on cellular viability. The levels of IL-6 and IL-8 were measured by ELISA. The expression of iNOS, COX-2, NF-κB, and LXRα were detected by western blot analysis. The results showed that glycyrrhizin significantly inhibited LPS-induced IL-6 and IL-8 production, as well as COX-2 and iNOS expression...
June 23, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28607067/a-recruiting-protein-of-geranylgeranyl-diphosphate-synthase-controls-metabolic-flux-toward-chlorophyll-biosynthesis-in-rice
#20
Fei Zhou, Cheng-Yuan Wang, Michael Gutensohn, Ling Jiang, Peng Zhang, Dabing Zhang, Natalia Dudareva, Shan Lu
In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
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