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https://www.readbyqxmd.com/read/28811616/synthesis-free-pet-imaging-of-brown-adipose-tissue-and-tspo-via-combination-of-disulfiram-and-64-cucl2
#1
Jing Yang, Jian Yang, Lu Wang, Anna Moore, Steven H Liang, Chongzhao Ran
PET imaging is a widely applicable but a very expensive technology. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18 kDa (TSPO) via a combination of disulfiram, an FDA approved drug for alcoholism, and (64)CuCl2 (termed (64)Cu-Dis). In this method, a step-wise injection protocol of (64)CuCl2 and disulfiram was used to accomplish the purpose of synthesis-free...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775204/impact-of-endothelial-tspo-on-the-quantification-of-18-f-dpa-714
#2
Catriona Wimberley, Sonia Lavisse, Vincent Brulon, Marie-Anne Peyronneau, Claire Leroy, Benedetta Bodini, Philippe Remy, Bruno Stankoff, Irene Buvat, Michel Bottlaender
(18)F-DPA-714 is a second generation tracer for positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging especially due to a basal expression of TSPO. The aim of this study was to evaluate a compartmental model which accounts for endothelial TSPO binding on PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent (18)F-DPA-714 PET scans with arterial blood sampling and metabolite analysis...
August 3, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28771957/bridging-pharmaceutical-chemistry-with-drug-and-nanoparticle-targeting-to-investigate-the-role-of-the-18-kda-translocator-protein-tspo
#3
REVIEW
Rosa Maria Iacobazzi, Antonio Lopalco, Annalisa Cutrignelli, Valentino Laquintana, Angela Lopedota, Massimo Franco, Nunzio Denora
An interesting mitochondrial biomarker is the 18-kDa mitochondrial translocator protein (TSPO). Decades of study have shown that this protein plays an important role in a wide range of cellular functions, including opening of the mitochondrial permeability transition pore as well as programmed cell death and proliferation. Variations in TSPO expression have been correlated to different diseases, from tumors to endocrine and neurological disorders. TSPO has therefore become an appealing target for both early diagnosis and selective mitochondrial drug delivery...
August 3, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28755381/molecular-modeling-of-transporters-from-low-resolution-cryo-electron-microscopy-map-to-conformational-exploration-the-example-of-tspo
#4
Aurore Vaitinadapoule, Catherine Etchebest
This chapter describes a protocol to establish a three-dimensional (3D) model of a protein and to explore its conformational landscape. It combines predictions from up-to-date bioinformatics methods with low-resolution experimental data. It also proposes to examine rapidly the dynamics of the protein using molecular dynamics simulations with a coarse-grained force field. Tools for analyzing these trajectories are suggested as well as those for constructing all-atoms models. Thus, starting from a protein sequence and using free software, the user can get important conformational information, which might improve the knowledge about the protein function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28755378/solid-state-nmr-of-membrane-protein-reconstituted-in-proteoliposomes-the-case-of-tspo
#5
Lucile Senicourt, Luminita Duma, Vassilios Papadopoulos, Jean-Jacques Lacapere
Structural studies of membrane proteins (MP) in a native or native-like environment remain a challenge. X-ray crystallography of three-dimensional crystals of MP in lipids and cryo-electron microscopy of two-dimensional crystals also in lipids have given atomic structures of several MP. Recent developments of solid-state NMR (ssNMR) provided structural data of MP in lipids and should give access to the dynamic behavior of MP's in a native-like environment. Preparation of samples for ssNMR is not trivial with overexpressed proteins since purified recombinant MP have to be reincorporated in proteoliposomes and concentrated in the small volume of the rotor used for ssNMR studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28755361/recombinant-overexpression-of-mammalian-tspo-isoforms-1-and-2
#6
Lucile Senicourt, Soria Iatmanen-Harbi, Claude Hattab, Mariano Anibal Ostuni, Marie-France Giraud, Jean-Jacques Lacapere
TSPO is a 18 kDa membrane protein that exists in mammalian as two isoforms 1 and 2. They are involved in different functions and are located in different membranes. TSPO1 is mainly located in outer mitochondrial membrane, whereas TSPO2 is encountered in plasma membrane of red blood cells. Determination of their structures is a milestone to understand their function. Their natural abundance is not sufficient to get large amounts usually required for structural studies. We described heterologous overexpression in both bacterial and cell-free system and purification on immobilized-metal affinity chromatography (IMAC) of both proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28754131/a-translocator-protein-18%C3%A2-kda-agonist-protects-against-cerebral-ischemia-reperfusion-injury
#7
Han-Dong Li, Minshu Li, Elaine Shi, Wei-Na Jin, Kristofer Wood, Rayna Gonzales, Qiang Liu
BACKGROUND: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28741281/microglial-depletion-and-activation-a-11-c-pbr28-pet-study-in-nonhuman-primates
#8
Ansel T Hillmer, Daniel Holden, Krista Fowles, Nabeel Nabulsi, Brian L West, Richard E Carson, Kelly P Cosgrove
BACKGROUND: The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging. The goal of this work was to assess two [(11)C]PBR28 imaging paradigms for measuring dynamic microglia changes in Macaca mulatta. METHODS: Dynamic [(11)C]PBR28 PET imaging data with arterial blood sampling were acquired to quantify TSPO levels as [(11)C]PBR28 V T. Scans were acquired at three timepoints: baseline, immediately post-drug, and prolonged post-drug...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28738332/neuroprogression-and-immune-activation-in-major-depressive-disorder
#9
Jeffrey H Meyer
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28733954/assessment-of-simplified-ratio-based-approaches-for-quantification-of-pet-11-c-pbr28-data
#10
Granville J Matheson, Pontus Plavén-Sigray, Anton Forsberg, Andrea Varrone, Lars Farde, Simon Cervenka
PURPOSE: Kinetic modelling with metabolite-corrected arterial plasma is considered the gold standard for quantification of [(11)C]PBR28 binding to the translocator protein (TSPO), since there is no brain region devoid of TSPO that can serve as reference. The high variability in binding observed using this method has motivated the use of simplified ratio-based approaches such as standardised uptake value ratios (SUVRs) and distribution volume (VT) ratios (DVRs); however, the reliability of these measures and their relationship to VT have not been sufficiently evaluated...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28705919/time-courses-of-cortical-glucose-metabolism-and-microglial-activity-across-the-life-span-of-wild-type-mice-a-pet-study
#11
Matthias Brendel, Carola Focke, Tanja Blume, Finn Peters, Maximilian Deussing, Federico Probst, Anna Jaworska, Felix Overhoff, Nathalie Albert, Simon Lindner, Barbara von Ungern-Sternberg, Peter Bartenstein, Christian Haass, Gernot Kleinberger, Jochen Herms, Axel Rominger
Contrary to findings in human brain, [(18)F]-FDG PET shows cerebral hypermetabolism of aged wild-type (WT) mice relative to younger animals, supposedly due to microglial activation. Therefore, we used dual tracer µPET to examine directly the link between neuroinflammation and hypermetabolism in aged mice. Methods: WT mice (5-20 months) were investigated in a cross-sectional design using [(18)F]-FDG (N = 43) and TSPO ([(18)F]-GE180; N = 58) µPET, with volume-of-interest and voxel-wise analyses. Biochemical analysis of plasma cytokine levels and immunohistochemical confirmation of microglial activity were also performed...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28701948/microglial-activation-in-traumatic-brain-injury
#12
REVIEW
Cornelius K Donat, Gregory Scott, Steve M Gentleman, Magdalena Sastre
Microglia have a variety of functions in the brain, including synaptic pruning, CNS repair and mediating the immune response against peripheral infection. Microglia rapidly become activated in response to CNS damage. Depending on the nature of the stimulus, microglia can take a number of activation states, which correspond to altered microglia morphology, gene expression and function. It has been reported that early microglia activation following traumatic brain injury (TBI) may contribute to the restoration of homeostasis in the brain...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28698896/the-role-of-tspo-pet-in-assessing-neuroinflammation
#13
Ania A Crawshaw, Neil P Robertson
No abstract text is available yet for this article.
August 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28698403/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#14
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stéphanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombès, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombès
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695372/increased-expression-of-translocator-protein-tspo-marks-pro-inflammatory-microglia-but-does-not-predict-neurodegeneration
#15
Lien Beckers, Dieter Ory, Ivana Geric, Lieven Declercq, Michel Koole, Michael Kassiou, Guy Bormans, Myriam Baes
PURPOSE: Activation of the innate immune system plays a significant role in pathologies of the central nervous system (CNS). In order to follow disease progression and evaluate effectiveness of potential treatments involved in neuroinflammation, it is important to track neuroinflammatory markers in vivo longitudinally. The translocator protein (TSPO) is used as a target to image neuroinflammation as its expression is upregulated in reactive glial cells during CNS pathologies. However, it remains unclear in which microglial phenotypes TSPO levels are upregulated, as microglia can display a plethora of activation states that can be protective or detrimental to the CNS...
July 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28675779/neurosteroidogenesis-and-progesterone-anti-inflammatory-neuroprotective-effects
#16
REVIEW
Alejandro F De Nicola, Laura I Garay, Maria Meyer, Rachida Guennoun, Regine Sitruk-Ware, Michael Schumacher, Maria Claudia Gonzalez Deniselle
Progesterone shows anti-inflammatory and promyelinating effects in mice with autoimmune experimental encephalomyelitis (EAE), a commonly used model for multiple sclerosis (MS). Since neurosteroids have been implicated as protective factors for MS and EAE, we analyzed the expression of neurosteroidogenic enzymes in the compromised spinal cord of EAE mice. EAE was induced in female C57Bl6 mice and killed on day 16 after induction. Progesterone was given by pellet implantation 1 week before EAE induction. Untreated EAE mice showed decreased mRNAs for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), cholesterol side-chain cleavage (P450scc), 5α-reductase, 3α-hydroxysteroid dehydrogenase (3α-HSOR) and aromatase, whereas changes of 3β-hydroxysteroid dehydrogenase (3β-HSD) were not significant...
July 4, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28667781/translocator-protein-18-kda-an-update-on-its-function-in-steroidogenesis
#17
REVIEW
Vassilios Papadopoulos, Jinjiang Fan, Barry Zirkin
Translocator protein (18 kDa), TSPO, is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localized to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis...
July 1, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28655607/overexpression-of-the-18%C3%A2-kda-translocator-protein-tspo-in-the-hippocampal-dentate-gyrus-produced-anxiolytic-and-antidepressant-like-behavioural-effects
#18
Lei Li, Wei Wang, Li-Ming Zhang, Xiang-Yun Jiang, Shu-Zheng Sun, Li-Jun Sun, Ying Guo, Jie Gong, You-Zhi Zhang, Heng-Lin Wang, Yun-Feng Li
The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression...
June 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28645478/a-tspo-ligand-prevents-mitochondrial-sterol-accumulation-and-dysfunction-during-myocardial-ischemia-reperfusion-in-hypercholesterolemic-rats
#19
Julien Musman, Stéphanie Paradis, Mathieu Panel, Sandrine Pons, Caroline Barau, Claudio Caccia, Valerio Leoni, Bijan Ghaleh, Didier Morin
A major cause of cell death during myocardial ischemia-reperfusion is mitochondrial dysfunction. We previously showed that the reperfusion of an ischemic myocardium was associated with an accumulation of cholesterol into mitochondria and a concomitant strong generation of auto-oxidized oxysterols. The inhibition of mitochondrial accumulation of cholesterol abolished the formation of oxysterols and prevented mitochondrial injury at reperfusion. The aim of this study was to investigate the impact of hypercholesterolemia on sterol and oxysterol accumulation in rat cardiac cytosols and mitochondria and to analyse the effect of the translocator protein ligand 4'-chlorodiazepam on this accumulation and mitochondrial function...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28640253/a-role-for-tspo-in-mitochondrial-ca-2-homeostasis-and-redox-stress-signaling
#20
Jemma Gatliff, Daniel A East, Aarti Singh, Maria Soledad Alvarez, Michele Frison, Ivana Matic, Caterina Ferraina, Natalie Sampson, Federico Turkheimer, Michelangelo Campanella
The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca(2+) signaling leading to a parallel increase in the cytosolic Ca(2+) pools that activate the Ca(2+)-dependent NADPH oxidase (NOX) thereby increasing ROS...
June 22, 2017: Cell Death & Disease
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