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https://www.readbyqxmd.com/read/29778664/gestational-diabetes-mellitus-modulates-cholesterol-homeostasis-in-human-fetoplacental-endothelium
#1
Yidan Sun, Susanne Kopp, Jasmin Strutz, Chaitanya Chakravarthi Gali, Martina Zandl-Lang, Elham Fanaee-Danesh, Andrijana Kirsch, Silvija Cvitic, Saša Frank, Richard Saffery, Ingemar Björkhem, Gernot Desoye, Christian Wadsack, Ute Panzenboeck
Gestational diabetes mellitus (GDM) is associated with excessive oxidative stress which may affect placental vascular function. Cholesterol homeostasis is crucial for maintaining fetoplacental endothelial function. We aimed to investigate whether and how GDM affects cholesterol metabolism in human fetoplacental endothelial cells (HPEC). HPEC were isolated from fetal term placental arterial vessels of GDM or control subjects. Cellular reactive oxygen species (ROS) were detected by H2 DCFDA fluorescent dye. Oxysterols were quantified by gas chromatography-mass spectrometry analysis...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29603559/enzymatic-formation-of-a-skipped-methyl-substituted-octaprenyl-side-chain-of-longestin-ks-505a-involvement-of-homo-ipp-as-a-common-extender-unit
#2
Taro Ozaki, Sandip S Shinde, Lei Gao, Ryo Okuizumi, Chengwei Liu, Yasushi Ogasawara, Xiaoguang Lei, Tohru Dairi, Atsushi Minami, Hideaki Oikawa
Longestin (KS-505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). The biochemical analysis of Lon23, a methyltransferase involved in the biosynthesis of longestin, demonstrated that methylation of IPP afforded 3Z-3-methyl IPP. This compound as well as IPP was selectively accepted as extender units by Lon22, a geranylgeranyl diphosphate (GGPP) synthase homolog, to yield dimethylated GGPP (dmGGPP)...
March 30, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29573196/efatutazone-and-t0901317-exert-synergistically-therapeutic-effects-in-acquired-gefitinib-resistant-lung-adenocarcinoma-cells
#3
Jie Ni, Lei-Lei Zhou, Li Ding, Xue-Qin Zhang, Xia Zhao, Huizi Li, Haixia Cao, Siwen Liu, Zhuo Wang, Rong Ma, Jianzhong Wu, Jifeng Feng
The development of acquired EGFR-TKI therapeutic resistance is still a serious clinical problem in the management of lung adenocarcinoma. Peroxisome proliferator activated receptor gamma (PPARγ) agonists may exhibit anti-tumor activity by transactivating genes which are closely associated with cell proliferation, apoptosis, and differentiation. However, it remains not clear whether efatutazone has similar roles in lung adenocarcinoma cells of gefitinib resistant such as HCC827-GR and PC9-GR. It has been demonstrated by us that efatutazone prominently increased the mRNA and protein expression of PPARγ, liver X receptor alpha (LXRα),as well as ATP binding cassette subfamily A member 1 (ABCA1)...
March 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29571724/puerarin-prevents-lps-induced-acute-lung-injury-via-inhibiting-inflammatory-response
#4
Xinye Wang, Jinjun Yan, Xiaohong Xu, Chunyan Duan, Zheng Xie, Zheqian Su, Hongxia Ma, Hui Ma, Xing Wei, Xiaochun Du
Acute lung injury (ALI) is a critical illness syndrome with high morbidity and mortality in patients. Inflammation has been known to be involved in the development of ALI. The purpose of this study was to investigate the effect of puerarin on lipopolysaccharide (LPS)-induced ALI in mice. The pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were determined by ELISA. Western blot analysis was used for detecting the expression of NF-κB, IκBα, and LXRα. And myeloperoxidase (MPO) activity, lung wet/dry (W/D) ratio, and histopathological examination were also detected in lung tissues...
March 20, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29532878/simvastatin-exerts-anticancer-effects-in-osteosarcoma-cell-lines-via-geranylgeranylation-and-c-jun-activation
#5
Shinwan Kany, Mathias Woschek, Niels Kneip, Ramona Sturm, Miriam Kalbitz, Marc Hanschen, Borna Relja
Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options and the underlying mechanisms is essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential and the underlying mechanisms in osteosarcoma is the subject of the present study. Human osteosarcoma cells (SaOS-2 and U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h...
April 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29523174/the-role-of-atorvastatin-in-suppressing-tumor-growth-of-uterine-fibroids
#6
Zhaojun Shen, Saisai Li, Bo Sheng, Qi Shen, Lu-Zhe Sun, Haiyan Zhu, Xueqiong Zhu
BACKGROUND: Medical therapeutic options remain quite limited for uterine fibroids treatment. Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have anti-tumoral effects on multiple cancer types, however, little is known about their effects on uterine fibroids. METHODS: Initially, we conducted a retrospective study of 120 patients with uterine fibroids and hyperlipidemia from the Second Affiliated Hospital of Wenzhou Medical University...
March 9, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29497895/preclinical-investigation-of-a-potent-geranylgeranyl-diphosphate-synthase-inhibitor
#7
Staci L Haney, Yashpal S Chhonker, Michelle L Varney, Geoffrey Talmon, Daryl J Murry, Sarah A Holstein
Geranylgeranyl diphosphate synthase (GGDPS) is the enzyme in the isoprenoid biosynthesis pathway that catalyzes the synthesis of the 20-carbon isoprenoid GGPP, which serves as the isoprenoid donor for protein geranylgeranylation reactions. Rab proteins mediate vesicle trafficking within the cell and their activity is dependent on geranylgeranylation. Our prior work has demonstrated that agents that disrupt Rab geranylgeranylation disrupt monoclonal protein trafficking in myeloma cells, resulting in induction of the unfolded protein response pathway and apoptosis...
March 2, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29476987/isoprenoids-and-tau-pathology-in-sporadic-alzheimer-s-disease
#8
Sandra Pelleieux, Cynthia Picard, Louise Lamarre-Théroux, Doris Dea, Valérie Leduc, Youla S Tsantrizos, Judes Poirier
The mevalonate pathway has been described to play a key role in Alzheimer's disease (AD) physiopathology. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are nonsterol isoprenoids derived from mevalonate, which serve as precursors to numerous human metabolites. They facilitate protein prenylation; hFPP and hGGPP synthases act as gateway enzymes to the prenylation of the small guanosine triphosphate (GTP)ase proteins such as RhoA and cdc42 that have been shown to facilitate phospho-tau (p-Tau, i...
May 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29444209/geranylgeranyl-pyrophosphate-synthase-facilitates-the-organization-of-cardiomyocytes-during-mid-gestation-through-modulating-protein-geranylgeranylation-in-mouse-heart
#9
Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, Chaojun Li
Aims: With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodeling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results: Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function...
February 12, 2018: Cardiovascular Research
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
#10
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
#11
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...
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
#12
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...
2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29236027/simvastatin-inhibits-cell-proliferation-and-migration-in-human-anaplastic-thyroid-cancer
#13
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
#14
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
#15
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
#16
Marc M Schumacher, Dong-Jae Jun, Brittany M Johnson, Russell A DeBose-Boyd
UBIAD1 (UbiA prenyltransferase domain-containing protein-1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2 We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized 3-hydroxy-3-methylglutaryl (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...
January 5, 2018: 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
#17
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
#18
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
#19
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
#20
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
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