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HMG-CoA reductase

Maria I Patrício, Alun R Barnard, Kanmin Xue, Robert E MacLaren
INTRODUCTION: Choroideremia is an X-linked inherited retinal degeneration that causes blindness in afflicted males by middle age. The causative gene, CHM, plays a key role in intracellular trafficking pathways, and its disruption impairs cell homeostasis. Areas covered: The mechanism by which mutations in CHM cause choroideremia is still under debate. Here we describe the molecular defects in choroideremia cells regarding both the deficiency of prenylation and the involvement of Rab GTPases...
June 22, 2018: Expert Opinion on Biological Therapy
Sean C Skeldon, Bruce Carleton, James Brophy, Mohit Sodhi, Mahyar Etminan
OBJECTIVE: Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (i.e. statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. DESIGN: Case control study. PATIENTS: A cohort of patients from a random sample of 9,053,240 US subjects from the PharMetrics Plus™ health claims database from 2006 to 2016 was created...
June 19, 2018: Clinical Endocrinology
Cancan Zhou, Zhenyan Gao, Ju Wang, Meiqin Wu, Shuang Hu, Fei Chen, Junxia Liu, Hui Pan, Chonghuai Yan
Lead exposure has been evidenced as a risk factor for Alzheimer's disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks...
June 14, 2018: Toxicology Letters
Yi Yang, Sinyi Kong, Yana Zhang, Johanna Melo-Cardenas, Beixue Gao, Yusi Zhang, Donna D Zhang, Bin Zhang, JianXun Song, Edward Thorp, Kezhong Zhang, Jinping Zhang, Deyu Fang
Humoral immunity involves multiple checkpoints that occur duringin B-cell development, maturation, and activation. The pre--B-cell receptor (pre-BCR) is expressed following the productive recombination of the immunoglobulin heavy- chain gene, and. sSignalsing through the pre-BCR are is required for the differentiation of pre-B cells into immature B cells. However, the molecular mechanisms controlling the pre-BCR expression and signaling strength remain undefined. Herein, we probed the role of the endoplasmic reticulum-associated, stress-activated E3 ubiquitin ligase HMG-CoA reductase degradation 1 (Hrd1) in B-cell differentiation...
June 15, 2018: Journal of Biological Chemistry
Ivan M Petyaev, Naylia A Zigangirova, Valeriy V Tsibezov, Elena Y Morgunova, Natalia E Bondareva, Nigel H Kyle, Yuriy K Bashmakov
Incubation of B10.MLM cells, a cell line of alveolar macrophages, with lycopene, a carotenoid, leads to an increase of lycopene content in their microsomal fraction. That increase was higher and developed faster when the cells were incubated with immune complexes formed by lycopene and mAb 6B9 (L-6B9 mAb), a monoclonal hapten-specific antibody raised against lycopene, as compared with dimethyl sulfoxide (DMSO)-dissolved lycopene (DMSO-L). Moreover, incubation of B10.MLM cells with L-6B9 mAb complexes was accompanied by more efficient accumulation of lipid droplets in the cultured cells and more significant inhibition of mRNA for 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase, a rate-limiting enzyme of cholesterol biosynthesis known to be targeted by lycopene...
June 14, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Zhihe Huo, Ying Kong, Mei Meng, Zhifei Cao, Quansheng Zhou
Vascular endothelial protein tyrosine phosphatase (VE-PTP) is essential for endothelial cells (ECs) adherens junction and vascular homeostasis; however, the regulatory mechanism of VE-PTP transcription is unknown, and a drug able to promote VE-PTP expression in ECs has not yet been reported in the literature. In this study, we used human ECs as a model to explore small molecule compounds able to promote VE-PTP expression, and found that atorvastatin, a HMG-CoA reductase inhibitor widely used in the clinic to treat hypercholesterolemia-related cardiovascular diseases, strongly promoted VE-PTP transcription in ECs through activating the VE-PTP promoter and upregulating the expression of the transcription factor, specificity protein 1 (SP1)...
June 9, 2018: Vascular Pharmacology
Peta Bradbury, Daniela Traini, Alaina J Ammit, Paul M Young, Hui Xin Ong
Despite many therapeutic advancements over the past decade, the continued rise in chronic inflammatory lung diseases incidence has driven the need to identify and develop new therapeutic strategies, with superior efficacy to treat these diseases. Statins are one class of drug that could potentially be repurposed as an alternative treatment for chronic lung diseases. They are currently used to treat hypercholesterolemia by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, that catalyses the rate limiting step in the mevalonate biosynthesis pathway, a key intermediate in cholesterol metabolism...
June 8, 2018: Advanced Drug Delivery Reviews
Tulsankar Sachin Laxman, Santosh Kumar Puttrevu, Rajesh Pradhan, Anjali Mishra, Sarvesh Verma, Yashpal S Chhonker, Swarnim Srivastava, Suriya P Singh, Koneni V Sashidhara, Rabi Sankar Bhatta
The present study was designed to investigate the oral bioavailability, metabolism, tissue disposition and excretion of 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09), a novel HMG-CoA reductase inhibitor in male Sprague Dawley (SD) rats. Tissue distribution, oral bioavailability and excretion studies of 4655K-09 were carried out in male SD rats through oral administration at active dose of 25 mg/kg. In vitro metabolism studies were carried out in different rat tissues S9 fractions to evaluate primary organs responsible for conversion of parent 4655K-09 to its major active metabolite K-9T...
June 6, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Nawal M Al-Rasheed, Nouf M Al-Rasheed, Yieldez A Bassiouni, Iman H Hasan, Maha A Al-Amin, Hanaa N Al-Ajmi, Ayman M Mahmoud
Statins are HMG-CoA reductase inhibitors with lipid-lowering effect and commonly used to reduce cardiovascular risk in diabetic patients. The present study investigates the ameliorative effect of simvastatin (SIM) on diabetic nephropathy in rats, pointing to its anti-apoptotic and anti-oxidative stress efficacies. Diabetes was induced by a single intraperitoneal injection of 55 mg/kg body weight streptozotocin (STZ) and both control and diabetic rats received 10 mg/kg SIM for 90 days. Treatment with SIM diminished the body weight loss, blood glucose and, serum creatinine, urea and uric acid in diabetic rats...
May 31, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Carlos F Araujo-Lima, Larissa S A Christoni, Graça Justo, Maria N C Soeiro, Claudia A F Aiub, Israel Felzenszwalb
Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and this class of drugs has been studied as protective agents against DNA damages. Alkylating agents (AAs) are able to induce alkylation in macromolecules, causing DNA damage, as DNA methylation. Our objective was to evaluate atorvastatin (AVA) antimutagenic, cytoprotective, and antigenotoxic potentials against DNA lesions caused by AA. AVA chemopreventive ability was evaluated using antimutagenicity assays ( Salmonella /microsome assay), cytotoxicity, cell cycle, and genotoxicity assays in HepG2 cells...
2018: Oxidative Medicine and Cellular Longevity
Md Wasimul Haque, Pritha Bose, Mohd Usman Mohd Siddique, Priyashree Sunita, Antonio Lapenna, Shakti P Pattanayak
AIM: 7,12-dimethylbenz(a)anthracene(DMBA), a PAH derivative initializes cascades of signaling events that alters a variety of enzymes responsible for lipid and glucose homeostasis resulting in enhanced availability and consumption of energy producing molecules for the development of carcinogenesis. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) is a key enzyme regulating the pathway of synthesis of cholesterol whereas liver-X-receptor (LXR) regulates lipid, carbohydrate metabolism in various malignancies including mammary carcinogenesis (MC)...
May 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lee-Ching Lew, Sy-Bing Choi, Boon-Yin Khoo, Sasidharan Sreenivasan, Kee-Leong Ong, Min-Tze Liong
Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells...
April 2018: Korean Journal for Food Science of Animal Resources
Jun Inoue, Shingo Miyata, Makoto Shimizu, Ryuichiro Sato
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate a wide variety of genes involved in fatty acid and cholesterol synthesis. In the present study, we identified that isoxanthohumol (IXN) suppressed SREBP activity. Low concentrations of IXN (10 and 30 μM) reduced the amount of mature forms of SREBPs, while high concentration of IXN (100 μM) reduced both precursor and mature forms of SREBPs in Huh-7 cells. The IXN-mediated decrease in the precursor forms of SREBPs in Huh-7 cells was completely abolished by culturing cells under sterol-supplemented conditions and was partly abolished by treatment with a proteasome inhibitor, MG132, but not a lysosome inhibitor, NH4 Cl...
May 26, 2018: Bioscience, Biotechnology, and Biochemistry
Yitian Guo, Hanwen Luo, Yimeng Wu, Jacques Magdalou, Liaobin Chen, Hui Wang
Epidemiological surveys suggest that adult hypercholesterolemia has an intrauterine origin and exhibits gender differences. Our previous study demonstrated that adult rats with intrauterine growth retardation (IUGR) offspring rats induced by prenatal caffeine exposure (PCE) had a higher serum total cholesterol (TCH) level. In this study, we aimed to analyze the influencing factors, underlying mechanism and interactions affecting hypercholesterolemia in adult offspring with caffeine exposure during pregnancy...
May 22, 2018: Reproductive Toxicology
Jill Campbell
No abstract text is available yet for this article.
June 2018: Journal of Perioperative Practice
Shuang Rong, Siqi Zhao, Xu Kai, Li Zhang, Yanting Zhao, Xiao Xiao, Wei Bao, Liegang Liu
The beneficial effects of red wine against cardiovascular disease are associated with the abundant antioxidant polyphenols such as procyanidins. Recently, procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins showed strong antioxidant activities in vitro, have been isolated and identified in our laboratory. The aim of present study was to investigate the anti-atherosclerotic effects of LPPC on atherosclerosis and hyperlipidemia in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet (HFD, 21% fat, 0...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
M S Sujith Kumar, Ibandalin Mawlong, Kishwar Ali, Aruna Tyagi
Plants respond to drought stress in the form of various physio-biochemical and molecular changes at both cellular and molecular levels. Drought stress causes the destruction of cell membranes by disintegration of membrane lipids. One of the major groups of membrane lipids that plays important role in preserving the integrity of cell membranes is phytosterols. HMG-CoA reductase (HMGR) is the principal enzyme in the biosynthesis of plant sterols, synthesized via mevalonic acid pathway. Phospholipid: sterol acyltransferase (PSAT) is another important enzyme that plays an important role in turnover of phytosterols into steryl esters and helps maintain homeostasis of membrane lipids...
May 15, 2018: Plant Physiology and Biochemistry: PPB
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
M Thiney, N Della Schiava, R Ecochard, P Feugier, P Lermusiaux, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme inhibitors (ACE) or Angiotensin receptor blockers (ARB), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk for cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events and additional vascular surgery in vascularized LE-PAD patients...
May 16, 2018: Annals of Vascular Surgery
Colin H Beckwitt, Keisuke Shiraha, Alan Wells
The HMG-CoA reductase inhibitors, statins, have been used as lipid lowering drugs for decades and several epidemiological studies suggest statin usage correlates with a decreased incidence of cancer specific mortality in patients. However, the mechanism of this mortality benefit remains unclear. Here, we demonstrate that statin drug lipophilicity and affinity for its target enzyme, HMGCR, determine their growth suppressive potency against various tumor cell lines. The lipophilic atorvastatin decreases cancer cell proliferation and survival in vitro...
2018: PloS One
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