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https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#1
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097495/the-expression-of-hypoxia-inducible-factor-1%C3%AE-gene-is-not-affected-by-low-oxygen-conditions-in-yellow-perch-perca-flavescens-juveniles
#2
Karolina Kwasek, Simona Rimoldi, Anna Giulia Cattaneo, Timothy Parker, Konrad Dabrowski, Genciana Terova
Hypoxia can affect various fish populations, including yellow perch Perca flavescens, which is an economically and ecologically important species in Lake Erie, a freshwater system that often experiences hypoxia in the hypolimnetic part of the lake. Fish, similarly to mammals, possess molecular oxygen sensor-hypoxia-inducible factor-1 (HIF-1), a transcription factor that can affect expression of many downstream genes related to animal growth and locomotion, protein synthesis, as well as ATP and amino acid metabolism...
January 18, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28096234/glutamate-oxaloacetate-transaminase-enables-anaplerotic-refilling-of-tca-cycle-intermediates-in-stroke-affected-brain
#3
Cameron Rink, Surya Gnyawali, Richard Stewart, Seth Teplitsky, Hallie Harris, Sashwati Roy, Chandan K Sen, Savita Khanna
Ischemic stroke results in excessive release of glutamate, which contributes to neuronal cell death. Here, we test the hypothesis that otherwise neurotoxic glutamate can be productively metabolized by glutamate oxaloacetate transaminase (GOT) to maintain cellular energetics and protect the brain from ischemic stroke injury. The GOT-dependent metabolism of glutamate was studied in primary neural cells and in stroke-affected C57-BL6 mice using magnetic resonance spectroscopy and GC-MS. Extracellular Glu sustained cell viability under hypoglycemic conditions and increased GOT-mediated metabolism in vitro Correction of stroke-induced hypoxia using supplemental oxygen in vivo lowered Glu levels as measured by (1)H magnetic resonance spectroscopy...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28095989/prolonged-k-deficiency-increases-intracellular-atp-cell-cycle-arrest-and-cell-death-in-renal-tubular-cells
#4
Kedsarin Fong-Ngern, Nardtaya Ausakunpipat, Nilubon Singhto, Kanyarat Sueksakit, Visith Thongboonkerd
BACKGROUND: Chronic potassium (K(+)) deficiency can cause renal damage namely hypokalemic nephropathy with unclear pathogenic mechanisms. In the present study, we investigated expression and functional alterations in renal tubular cells induced by prolonged K(+) deficiency. METHODS: MDCK cells were maintained in normal-K(+) (CNK) (K(+)=5.3mmol/L), low-K(+) (CLK) (K(+)=2.5mmol/L), or K(+)-depleted (CKD) (K(+)=0mmol/L) medium for 10days (n=5 independent cultures/condition)...
January 4, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28090279/association-of-atp-binding-cassette-transporter-a1-abca1-565-c-t-gene-polymorphism-with-hypoalphalipoproteinemia-and-serum-lipids-il-6-and-crp-levels
#5
Mohammad Mahdi Babashamsi, Sohrab Halalkhor, Hamid Moradi Firouzjah, Hadi Parsian, Seyed Farzad Jalali, Mohammad Babashamsi
BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) is a membrane integral protein which plays a vital role in High Density Lipoprotein (HDL) metabolism and exerts a protective effect against Hypoalphalipoproteinemia (HA) by mediation of rate-limiting step in HDL biogenesis. In addition, this protein possesses anti-inflammatory effects by inhibiting the production of some inflammatory cytokines in macrophages. This study investigated the association of ABCA1-565 C/T gene polymorphism with HA and serum lipids, IL-6 and CRP levels...
January 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28088425/short-communication-staphylococcus-aureus-infection-modulates-expression-of-drug-transporters-and-inflammatory-biomarkers-in-mouse-mammary-gland
#6
A Oskarsson, Y Yagdiran, S Nazemi, J Tallkvist, C H Knight
Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands...
January 11, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28087358/vascular-calcification-abrogates-the-nicorandil-mediated-cardio-protection-in-ischemia-reperfusion-injury-of-rat-heart
#7
Sriram Ravindran, Jeyashri Murali, Sunil Kumar Amirthalingam, Senthilkumar Gopalakrishnan, Gino A Kurian
The present study was aimed to determine the efficacy of nicorandil in treating cardiac reperfusion injury with an underlying co-morbidity of vascular calcification (VC). Adenine diet was used to induce VC in Wistar rat and the heart was isolated to induce global ischemia reperfusion (IR) by Langendorff method, with and without the nicorandil (7.5mg/kg) pre-treatment and compared with those fed on normal diet. The adenine-treated rats displayed abnormal ECG changes and altered mitochondrial integrity compared to a normal rat heart...
January 10, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28087336/oleate-induces-katp-channel-dependent-hyperpolarisation-in-mouse-hypothalamic-glucose-excited-neurones-without-altering-cellular-energy-charge
#8
Selma Dadak, Craig Beall, Julia M Vlachaki Walker, Marc Pm Soutar, Rory J McCrimmon, Michael L J Ashford
The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurones) and mouse arcuate nucleus (ARC) neurones. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate and glucose sensing properties of mouse hypothalamic neurones...
January 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28080323/oral-adenosine-5-triphosphate-atp-administration-increases-postexercise-atp-levels-muscle-excitability-and-athletic-performance-following-a-repeated-sprint-bout
#9
Martin Purpura, John A Rathmacher, Matthew H Sharp, Ryan P Lowery, Kevin A Shields, Jeremy M Partl, Jacob M Wilson, Ralf Jäger
OBJECTIVE: Oral adenosine-5'-triphosphate (ATP) administration has failed to increase plasma ATP levels; however, chronic supplementation with ATP has shown to increase power, strength, lean body mass, and blood flow in trained athletes. The purpose of this study was to investigate the effects of ATP supplementation on postexercise ATP levels and on muscle activation and excitability and power following a repeated sprint bout. METHODS: In a double-blind, placebo-controlled, randomized design, 42 healthy male individuals were given either 400 mg of ATP as disodium salt or placebo for 2 weeks prior to an exercise bout...
January 12, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28079567/cardiac-calcium-release-channel-ryanodine-receptor-2-regulation-by-halogenated-anesthetics
#10
Derek R Laver, John Attia, Christopher Oldmeadow, Anthony W Quail
BACKGROUND: Halogenated anesthetics activate cardiac ryanodine receptor 2-mediated sarcoplasmic reticulum Ca release, leading to sarcoplasmic reticulum Ca depletion, reduced cardiac function, and providing cell protection against ischemia-reperfusion injury. Anesthetic activation of ryanodine receptor 2 is poorly defined, leaving aspects of the protective mechanism uncertain. METHODS: Ryanodine receptor 2 from the sheep heart was incorporated into artificial lipid bilayers, and their gating properties were measured in response to five halogenated anesthetics...
January 12, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28079299/a-platinum-blue-complex-exerts-its-cytotoxic-activity-via-dna-damage-and-induces-apoptosis-in-cancer-cells
#11
Zelal Adiguzel, Seniz Ozalp-Yaman, Gokalp Celik, Safia Salem, Tugba Bagci-Onder, Filiz Senbabaoglu, Yüksel Cetin, Ceyda Acilan
Here, we describe the characteristics of a Pt-blue complex [Pt4 (2-atp)8 (H2 O)(OH)] (2-atp: 2-aminothiophenol) as a prodrug for its DNA-binding properties and its use in cancer therapy. The nature of the interaction between the Pt-blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single and double stranded breaks (DBS) on DNA in vitro, but no DSBs in cells...
January 12, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28076802/peldor-spectroscopy-reveals-two-defined-states-of-a-sialic-acid-trap-transporter-sbp-in-solution
#12
Janin Glaenzer, Martin F Peter, Gavin H Thomas, Gregor Hagelueken
The tripartite ATP-independent periplasmic (TRAP) transporters are a widespread class of membrane transporters in bacteria and archaea. Typical substrates for TRAP transporters are organic acids including the sialic acid N-acetylneuraminic acid. The substrate binding proteins (SBP) of TRAP transporters are the best studied component and are responsible for initial high-affinity substrate binding. To better understand the dynamics of the ligand binding process, pulsed electron-electron double resonance (PELDOR, also known as DEER) spectroscopy was applied to study the conformational changes in the N-acetylneuraminic acid-specific SBP VcSiaP...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28074977/-association-of-c-reactive-protein-levels-with-metabolic-syndrome-in-adults-a-population-based-study
#13
Patricia Bustos, Bernardita Rosas, Pablo Román, Juan Villagrán, Hugo Amigo
BACKGROUND: Metabolic syndrome is highly prevalent among adults in Chile and represents a health risk. AIM: To determine the relationship between metabolic syndrome (MetS) and its components, with C reactive protein levels (CRP) as an inflammation marker. MATERIAL AND METHODS: The population studied consisted of 736 individuals born in a hospital from Valparaíso Region, aged between 32-38 years at the time of the study. MetS was identified according to the Adult Treatment Panel (ATP) III guidelines and inflammation was measured using ultra-sensitive CRP...
October 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28072760/pentoxifylline-inhibits-tlr-and-inflammasome-mediated-in-vitro-inflammatory-cytokine-production-in-human-blood-with-greater-efficacy-and-potency-in-newborns
#14
Esther M Speer, David J Dowling, Lukasz S Ozog, Jianjin Xu, Jie Yang, Geetika Kennady, Ofer Levy
BACKGROUND: Toll-like receptor (TLR)-mediated inflammation may contribute to neonatal sepsis, for which pentoxifylline (PTX), a phosphodiesterase inhibitor that raises intracellular cAMP, is a candidate adjunctive therapy. We characterized the anti-inflammatory effects of PTX towards TLR-mediated production of inflammatory (TNF, IL-1ß) and pro-resolution (IL-6, IL- 10) cytokines in human newborn and adult blood. METHODS: Newborn cord and adult blood were treated with PTX (50 - 400 μM) before, during or after stimulation with LPS (TLR4 agonist), R848 (TLR7/8 agonist) or LPS/ATP (inflammasome activation)...
January 10, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28069792/targeting-ent1-and-adenosine-tone-for-the-treatment-of-huntington-s-disease
#15
Yu-Han Kao, Meng-Syuan Lin, Chiung-Mei Chen, Yih-Ru Wu, Hui-Mei Chen, Hsing-Lin Lai, Yijuang Chern, Chun-Jung Lin
Huntington's disease (HD) is caused by an abnormal CAG expansion in the exon 1 of huntingtin gene. The treatment of HD is an unmet medical need. Given the important role of adenosine in modulating brain activity, in this study, levels of adenosine and adenine nucleotides in the cerebral spinal fluid of patients with HD and in the brain of two mouse models of HD (R6/2 and Hdh(150Q)) were analysed. The expression and activity of ENT1 in the striatum of mice with HD were measured. Targeting adenosine tone for treating HD was examined in R6/2 mice by genetic removal of ENT1 and by giving an ENT1 inhibitor, respectively...
January 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#16
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway are, however, poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28065674/mitochondria-in-teleost-spermatozoa
#17
REVIEW
Patricio Ulloa-Rodríguez, Elías Figueroa, Rommy Díaz, Manuel Lee-Estevez, Stefania Short, Jorge G Farías
There is an extraordinary diversity of reproductive modes in teleost and this variability is related to the phylogenetic relationships and adaption to very different biotopes. As in all vertebrates, sperm is produced as the end product of the process of spermatogenesis, and regarding teleost the spermatozoa lack an acrosome in almost all species and motility is activated as a response to osmolarity and ion content of the aquatic medium where the sperm is released. In this context, mitochondria possess a fundamental role for fish spermatozoa motility and integrity, hence, fertilizing potential; they are the energy supplier that allows flagellar movement and their dysfunction could play a main role in structural and functional damage to the spermatozoa...
January 5, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28064403/knockdown-of-clusterin-alters-mitochondrial-dynamics-facilitates-necrosis-in-camptothecin-induced-cancer-stem-cells
#18
Parthasarathy Arumugam, Annie Samson, Jieun Ki, Joon Myong Song
The existence of a well-established drug resistance mechanism in cancer stem cells (CSC) complicates the cancer treatment. Clusterin (CLU) plays a key role in maintaining the integrity of endoplasmic reticulum (ER) during drug-induced stress. Hence, silencing the CLU could significantly reduce the inherent drug resistance mechanism of CSC. The combination of drug-induced cytotoxicity, as well as the suppression of drug resistance in CSC, could circumvent the recurrence capability of the tumor. In the present study, camptothecin (CPT)-induced apoptosis and necrosis in CSC with and without siCLU treatment were simultaneously measured using Qdot-based total internal reflection fluorescence microscope (TIRF)...
January 7, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28062941/the-effects-of-ph-and-pco2-on-photosynthesis-and-respiration-in-the-diatom-thalassiosira-weissflogii
#19
Johanna A L Goldman, Michael L Bender, François M M Morel
The response of marine phytoplankton to the ongoing increase in atmospheric pCO2 reflects the consequences of both increased CO2 concentration and decreased pH in surface seawater. In the model diatom Thalassiosira weissflogii, we explored the effects of varying pCO2 and pH, independently and in concert, on photosynthesis and respiration by incubating samples in water enriched in H2(18)O. In long-term experiments (~6-h) at saturating light intensity, we observed no effects of pH or pCO2 on growth rate, photosynthesis or respiration...
January 6, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28062459/biofilm-composition-and-threshold-concentration-for-growth-of-legionella-pneumophila-on-surfaces-exposed-to-flowing-warm-tap-water-without-disinfectant
#20
Dick van der Kooij, Geo L Bakker, Ronald Italiaander, Harm R Veenendaal, Bart A Wullings
: Legionella pneumophila in potable-water installations poses a potential health risk, but quantitative information about its replication in biofilms in relation to water quality is scarce. Therefore, biofilm formation on surfaces of glass and chlorinated polyvinyl chloride (CPVC) in contact with tap water at 34-39°C was investigated under controlled hydraulic conditions in a model system inoculated with biofilm-grown L. pneumophila The biofilm on glass (average steady-state concentration: 23 ± 9 pg ATP cm(-2)) exposed to treated aerobic groundwater [0...
January 6, 2017: Applied and Environmental Microbiology
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