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Jing-Lu Jin, Yuan-Lin Guo, Jian-Jun Li
Apoprotein C-III (apoC-III), originating from the apoA-I/C-III/A-IV gene cluster affected by multiple regulating factors, has been demonstrated to have a validated link with hypertriglyceridemia in humans. Following genome studies establishing the impact of apoC-III on both plasma triglyceride (TG) level and cardiovascular disease (CVD), apoC-III offers us a novel explanation attempting to resolve the long-existing confusion with regard to the atherogenic effect of TG. Notably, apoC-III exerts its atherogenic effect by means of not only intervening in the function and metabolism of various lipid molecules, but also accelerating pro-inflammatory effects between monocytes and endothelial cells...
September 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Danit Ariel, Sun H Kim, Alice Liu, Fahim Abbasi, Cindy A Lamendola, Kaylene Grove, Vanessa Tomasso, Gerald M Reaven
BACKGROUND AND OBJECTIVE: Although salsalate administration consistently lowers plasma triglyceride concentrations in patients with type II diabetes, prediabetes, and/or insulin resistance, changes in low-density lipoprotein cholesterol (LDL-C) concentrations have been inconsistent; varying from no change to a significant increase. To evaluate the clinical relevance of this discordance in more detail, we directly measured LDL-C and obtained a comprehensive assessment of changes in lipid, lipoprotein, and apoprotein concentrations associated with salsalate use in insulin-resistant individuals, overweight or obese, but without diabetes, using vertical auto profile method...
September 2015: Journal of Clinical Lipidology
Koichiro Homma, Yasuhiko Homma, Tadashi Yoshida, Hideki Ozawa, Yutaka Shiina, Shu Wakino, Koichi Hayashi, Hiroshi Itoh, Shingo Hori
BACKGROUND: Plasma levels of low-density lipoproteins (LDLs) are decreased through stimulation of their hepatic uptake by statins via an LDL receptor. However, it is unclear whether statins equally stimulate the hepatic uptake of all LDL subfractions. OBJECTIVE: We compared the effects of atorvastatin on 3 LDL subfractions, and their associations with LDL-receptor activities, in Japanese patients with polygenic hypercholesterolemia (PHC), familial combined hyperlipoproteinemia (FCHL), and familial hypercholesterolemia (FH)...
March 2015: Journal of Clinical Lipidology
Bing Sun, Yuan Xie, Jinfa Jiang, Yiping Wang, Xiaolin Xu, Cuimei Zhao, Feifei Huang
BACKGROUND: Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. METHODS: Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks...
2015: Lipids in Health and Disease
Anping Cai, Guang Li, Jiyan Chen, Xida Li, Liwen Li, Yingling Zhou
BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD). METHODS: Totally 781 participants were enrolled and performed coronary angiography (CAG) to figure out the number of coronary artery stenosis. According to clinical presentation, electrocardiography, cardiac biomarker, and CAG result, participants were divided into control (excluded CAD), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) groups...
2015: BMC Cardiovascular Disorders
Jens N Lohscheider, Marc C Rojas-Stütz, Maxi Rothbart, Ulrica Andersson, Dietmar Funck, Kurt Mendgen, Bernhard Grimm, Iwona Adamska
Light-harvesting complex (LHC)-like (LIL) proteins contain two transmembrane helices of which the first bears a chlorophyll (Chl)-binding motif. They are widespread in photosynthetic organisms, but almost nothing is known about their expression and physiological functions. We show that two LIL3 paralogues (LIL3:1 and LIL3:2) in Arabidopsis thaliana are expressed in photosynthetically active tissues and their expression is differentially influenced by light stress. Localization studies demonstrate that both isoforms are associated with subcomplexes of LHC antenna of photosystem II...
October 2015: Plant, Cell & Environment
Jefferson S Plegaria, Stephen P Dzul, Erik R P Zuiderweg, Timothy L Stemmler, Vincent L Pecoraro
De novo protein design is a biologically relevant approach that provides a novel process in elucidating protein folding and modeling the metal centers of metalloproteins in a completely unrelated or simplified fold. An integral step in de novo protein design is the establishment of a well-folded scaffold with one conformation, which is a fundamental characteristic of many native proteins. Here, we report the NMR solution structure of apo α3DIV at pH 7.0, a de novo designed three-helix bundle peptide containing a triscysteine motif (Cys18, Cys28, and Cys67) that binds toxic heavy metals...
May 12, 2015: Biochemistry
Ying Liu, Douglas M Templeton
The kidney plays an important role in iron homeostasis and actively reabsorbs citrate. The bifunctional iron-regulatory protein IRP-1 potentially regulates iron trafficking and participates in citrate metabolism as a cytosolic (c-) aconitase. We investigated the role of cellular iron status in determining the expression and dynamics of IRP-1 in two renal cell types, with the aim of identifying a role of the protein in cellular ROS levels, citrate metabolism and glutamate production. The effects of iron supplementation and chelation on IRP-1 protein and mRNA levels and protein turnover were compared in cultured primary rat mesangial cells and a porcine renal tubule cell line (LLC-PK1)...
May 2015: Metallomics: Integrated Biometal Science
Renate Gessmann, Maria Papadovasilaki, Evangelos Drougkas, Kyriacos Petratos
The copper(II) centre of the blue copper protein pseudoazurin from Alcaligenes faecalis has been substituted by zinc(II) via denaturing the protein, chelation and removal of copper and refolding the apoprotein, followed by the addition of an aqueous solution of ZnCl2. Vapour-diffusion experiments produced colourless hexagonal crystals (space group P65), which when cryocooled had unit-cell parameters a=b=49.01, c=98.08 Å. Diffraction data collected at 100 K using a copper sealed tube were phased by the weak anomalous signal of five S atoms and one Zn atom...
January 1, 2015: Acta Crystallographica. Section F, Structural Biology Communications
Da Eun Lee, Soo Yeon Park, So Yun Park, Sa Ra Lee, Hye Won Chung, Kyungah Jeong
OBJECTIVES: The aim of this study was to investigate the clinical and biochemical profiles according to homeostasis model assessment of insulin resistance (HOMA-IR) in Korean polycystic ovary syndrome (PCOS) patients. METHODS: In 458 PCOS patients diagnosed by the Rotterdam European Society for Human Reproduction and Embryology (ESHRE) criteria, measurements of somatometry, blood test of hormones, glucose metabolic and lipid profiles, and transvaginal or transrectal ultrasonogram were carried out...
December 2014: Journal of Menopausal Medicine
Michael A Goren, Takefumi Morizumi, Indu Menon, Jeremiah S Joseph, Jeremy S Dittman, Vadim Cherezov, Raymond C Stevens, Oliver P Ernst, Anant K Menon
Opsin, the rhodopsin apoprotein, was recently shown to be an ATP-independent flippase (or scramblase) that equilibrates phospholipids across photoreceptor disc membranes in mammalian retina, a process required for disc homoeostasis. Here we show that scrambling is a constitutive activity of rhodopsin, distinct from its light-sensing function. Upon reconstitution into vesicles, discrete conformational states of the protein (rhodopsin, a metarhodopsin II-mimic, and two forms of opsin) facilitated rapid (>10,000 phospholipids per protein per second) scrambling of phospholipid probes...
2014: Nature Communications
Ibrahim Njimona, Rui Yang, Tilman Lamparter
Bacteriophytochromes (BphPs) are light-sensing regulatory proteins encoded in photosynthetic and non-photosynthetic bacteria. This protein class incorporate bilin as their chromophore, with majority of them bearing a light- regulated His kinase or His kinase related module in the C-terminal. We studied the His kinase actives in the temperature range of 5°C to 40°C on two BphPs, Agp1 from Agrobacterium tumefaciens and Cph1 from cyanobacterium Synechocystis PCC 6803. As reported, the phosphorylation activities of the far red (FR) irradiated form of the holoprotein is stronger than that of the red (R) irradiated form in both phytochromes...
2014: PloS One
Stefanie Stieb, Ziv Roth, Christina Dal Magro, Sabine Fischer, Eric Butz, Amir Sagi, Isam Khalaila, Bernhard Lieb, Sven Schenk, Ulrich Hoeger
The novel discoidal lipoprotein (dLp) recently detected in the crayfish, differs from other crustacean lipoproteins in its large size, apoprotein composition and high lipid binding capacity, We identified the dLp sequence by transcriptome analyses of the hepatopancreas and mass spectrometry. Further de novo assembly of the NGS data followed by BLAST searches using the sequence of the high density lipoprotein/1-glucan binding protein (HDL-BGBP) of Astacus leptodactylus as query revealed a putative precursor molecule with an open reading frame of 14...
December 2014: Biochimica et Biophysica Acta
Li-Feng Hong, Bo Yang, Song-Hui Luo, Jian-Jun Li
BACKGROUND: Revascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein (HDL) particle size (eHDL-S), the ratio of HDL cholesterol (HDL-C) to apoprotein A-I (apoA-I), is associated with the clinical outcomes of diabetic patients with stable coronary artery disease (CAD). METHODS: We performed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography...
September 2014: Journal of Geriatric Cardiology: JGC
Diederik F van Wijk, Barbara Sjouke, Amparo Figueroa, Hamed Emami, Fleur M van der Valk, Megan H MacNabb, Linda C Hemphill, Dominik M Schulte, Marion G Koopman, Mark E Lobatto, Hein J Verberne, Zahi A Fayad, John J P Kastelein, Willem J M Mulder, G Kees Hovingh, Ahmed Tawakol, Erik S G Stroes
BACKGROUND: Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk. OBJECTIVES: This study used (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) to investigate whether arterial inflammation is higher in patients with FH and, moreover, whether lipoprotein apheresis attenuates arterial wall inflammation in FH patients...
October 7, 2014: Journal of the American College of Cardiology
Brooke M Rock, Shawna M Hengel, Dan A Rock, Larry C Wienkers, Kent L Kunze
Ritonavir is a human immunodeficiency virus (HIV) protease inhibitor and an inhibitor of cytochrome P450 3A4, the major human hepatic drug-metabolizing enzyme. Given the potent inhibition of CYP3A4 by ritonavir, subtherapeutic doses of ritonavir are used to increase plasma concentrations of other HIV drugs oxidized by CYP3A4, thereby extending their clinical efficacy. However, the mechanism of inhibition of CYP3A4 by ritonavir remains unclear. To date, data suggests multiple types of inhibition by ritonavir, including mechanism-based inactivation by metabolic-intermediate complex formation, competitive inhibition, irreversible type II coordination to the heme iron, and more recently heme destruction...
December 2014: Molecular Pharmacology
Donghak Kim, Gun-Su Cha, Leslie D Nagy, Chul-Ho Yun, F Peter Guengerich
Cytochrome P450 (P450) 4A11 is the only functionally active subfamily 4A P450 in humans. P450 4A11 catalyzes mainly ω-hydroxylation of fatty acids in liver and kidney; this process is not a major degradative pathway, but at least one product, 20-hydroxyeicosatetraenoic acid, has important signaling properties. We studied catalysis by P450 4A11 and the issue of rate-limiting steps using lauric acid ω-hydroxylation, a prototypic substrate for this enzyme. Some individual reaction steps were studied using pre-steady-state kinetic approaches...
October 7, 2014: Biochemistry
Saurabh Kumar Pandey, David Řeha, Vasilina Zayats, Milan Melichercik, Jannette Carey, Rüdiger Ettrich
Arginine repressor of E. coli is a multifunctional hexameric protein that provides feedback regulation of arginine metabolism upon activation by the negatively cooperative binding of L-arginine. Interpretation of this complex system requires an understanding of the protein's conformational landscape. The ~50 kDa hexameric C-terminal domain was studied by 100 ns molecular dynamics simulations in the presence and absence of the six L-arg ligands that bind at the trimer-trimer interface. A rotational shift between trimers followed by rotational oscillation occurs in the production phase of the simulations only when L-arg is absent...
July 2014: Journal of Molecular Modeling
Giovanni Grandi, Ilaria Piacenti, Annibale Volpe, Angelo Cagnacci
AIM: To observe the influence on metabolism and body composition of two oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol (EE). STUDY DESIGN: Women on hormonal contraception with estradiol valerate (E2V)/dienogest (DNG) in a quadriphasic regimen (n = 16) or 30 μg EE/2 mg chlormadinone acetate (CMA) (n = 16) in a monophasic regimen were evaluated at the third cycle for modifications in lipoproteins, apoproteins and homeostatic model assessment for insulin resistance (HOMA-IR), and at the sixth cycle for body composition and the markers of bone turnover osteocalcin and C-telopeptide X...
September 2014: Gynecological Endocrinology
Marcin Barylski, Peter P Toth, Dragana Nikolic, Maciej Banach, Manfredi Rizzo, Giuseppe Montalto
High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury...
June 2014: Best Practice & Research. Clinical Endocrinology & Metabolism
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