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https://www.readbyqxmd.com/read/29678775/involvement-of-gap-junctions-in-astrocyte-impairment-induced-by-manganese-exposure
#1
Cailing Lu, Zhijuan Meng, Yiyuan He, Deqiang Xiao, Haiqing Cai, Yilu Xu, Xianghong Liu, Xinhang Wang, Laiming Mo, Ziwei Liang, Xuejing Wei, Qingqing Ao, Boying Liang, Xiyi Li, Shen Tang, Songchao Guo
Glutamate excitotoxicity, characterized as excessive glutamate stress, is considered to be involved in cerebral ischaemia, brain trauma, and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Glutamate homeostasis disruption was highlighted in Mn neurotoxicity caused by high levels of Mn. Astrocytes, accounting for approximately 50% of the neuronal cells in the central nervous system and maintain glutamate homeostasis, are sensitive to neurotoxicity induced by Mn exposure. Astrocytes are tightly coupled with gap junctions (GJ), which are comprised of connexins, mainly connexin43 (Cx43)...
April 17, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29677222/understanding-the-impact-of-the-cofactor-swapping-of-isocitrate-dehydrogenase-over-the-growth-phenotype-of-escherichia-coli-on-acetate-by-using-constraint-based-modeling
#2
Erick Armingol, Eduardo Tobar, Ricardo Cabrera
It has been proposed that NADP+-specificity of isocitrate dehydrogenase (ICDH) evolved as an adaptation of microorganisms to grow on acetate as the sole source of carbon and energy. In Escherichia coli, changing the cofactor specificity of ICDH from NADP+ to NAD+ (cofactor swapping) decreases the growth rate on acetate. However, the metabolic basis of this phenotype has not been analyzed. In this work, we used constraint-based modeling to investigate the effect of the cofactor swapping of ICDH in terms of energy production, response of alternative sources of NADPH, and partitioning of fluxes between ICDH and isocitrate lyase (ICL) -a crucial bifurcation when the bacterium grows on acetate-...
2018: PloS One
https://www.readbyqxmd.com/read/29675184/high-affinity-and-selective-detection-of-pyrophosphate-in-water-by-a-resorcinarene-salt-receptor
#3
Ngong Kodiah Beyeh, Isabel Díez, S Maryamdokht Taimoory, Daniel Meister, Andrew I Feig, John F Trant, Robin H A Ras, Kari Rissanen
Pyrophosphate (PPi) is a byproduct of DNA and RNA synthesis, and abnormal levels are indicative of disease. We report the high-affinity binding of PPi in water by N -alkyl ammonium resorcinarene chloride receptors. Experimental analysis using 1 H and 31 P NMR, isothermal titration calorimetry, mass spectrometry, and UV-vis spectroscopy all support exceptional selectivity of these systems for PPi in water. The measured affinity of K 1 = 1.60 × 107 M-1 for PPi is three orders of magnitude larger than that observed for binding to another phosphate, ATP...
February 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29673908/mechanism-underlying-the-contractile-activity-of-utp-in-the-mammalian-heart
#4
Ulrich Gergs, Daniel Rothkirch, Britt Hofmann, Hendrik Treede, Bernard Robaye, Andreas Simm, Christa E Müller, Joachim Neumann
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...
April 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29669923/a-folding-nucleus-and-minimal-atp-binding-domain-of-hsp70-identified-by-single-molecule-force-spectroscopy
#5
Daniela Bauer, Sarah Meinhold, Roman P Jakob, Johannes Stigler, Ulrich Merkel, Timm Maier, Matthias Rief, Gabriel Žoldák
The folding pathways of large proteins are complex, with many of them requiring the aid of chaperones and others folding spontaneously. Along the folding pathways, partially folded intermediates are frequently populated; their role in the driving of the folding process is unclear. The structures of these intermediates are generally not amenable to high-resolution structural techniques because of their transient nature. Here we employed single-molecule force measurements to scrutinize the hierarchy of intermediate structures along the folding pathway of the nucleotide binding domain (NBD) of Escherichia coli Hsp70 DnaK...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666623/autoimmunity-to-tropomyosin-specific-peptides-induced-by-mycobacterium-leprae-in-leprosy-patients-identification-of-mimicking-proteins
#6
Itu Singh, Asha Ram Yadav, Keshar Kunja Mohanty, Kiran Katoch, Prashant Sharma, Vinay Kumar Pathak, Deepa Bisht, Umesh D Gupta, Utpal Sengupta
Background: It has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy. Objectives: In this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666215/control-of-pancreatic-%C3%AE-cell-bioenergetics
#7
REVIEW
Charles Affourtit, Ben Alberts, Jonathan Barlow, Jane E Carré, Anthony G Wynne
The canonical model of glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells predicts a glucose-induced rise in the cytosolic ATP/ADP ratio. Such bioenergetic sensitivity to metabolic fuel is unusual as it implies that ATP flux is governed, to a significant extent, by ATP supply, while it is predominantly demand-driven in other cell types. Metabolic control is generally shared between different processes, but potential control of ATP consumption over β-cell bioenergetics has been largely ignored to date...
April 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29666184/atp-sensitive-potassium-channels-in-the-sinoatrial-node-contribute-to-heart-rate-control-and-adaptation-to-hypoxia
#8
Qadeer Aziz, Malcolm Finlay, David Montaigne, Leona Ojake, Yiwen Li, Naomi Anderson, Andreas Ludwig, Andrew Tinker
ATP-sensitive potassium channels (KATP ) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN)...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29662209/dynamic-coupling-between-conformations-and-nucleotide-states-in-dna-gyrase
#9
Aakash Basu, Matthew Hobson, Paul Lebel, Louis E Fernandes, Elsa M Tretter, James M Berger, Zev Bryant
Gyrase is an essential bacterial molecular motor that supercoils DNA using a conformational cycle in which chiral wrapping of > 100 base pairs confers directionality on topoisomerization. To understand the mechanism of this nucleoprotein machine, global structural transitions must be mapped onto the nucleotide cycle of ATP binding, hydrolysis and product release. Here we investigate coupling mechanisms using single-molecule tracking of DNA rotation and contraction during Escherichia coli gyrase activity under varying nucleotide conditions...
April 16, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29661379/isoflurane-disrupts-excitatory-neurotransmitter-dynamics-via-inhibition-of-mitochondrial-complex-i
#10
P I Zimin, C B Woods, E B Kayser, J M Ramirez, P G Morgan, M M Sedensky
BACKGROUND: The mechanisms of action of volatile anaesthetics are unclear. Volatile anaesthetics selectively inhibit complex I in the mitochondrial respiratory chain. Mice in which the mitochondrial complex I subunit NDUFS4 is knocked out [Ndufs4(KO)] either globally or in glutamatergic neurons are hypersensitive to volatile anaesthetics. The volatile anaesthetic isoflurane selectively decreases the frequency of spontaneous excitatory events in hippocampal slices from Ndufs4(KO) mice...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#11
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29653124/doxorubicin-triggers-bioenergetic-failure-and-p53-activation-in-mouse-stem-cell-derived-cardiomyocytes
#12
Teresa Cunha-Oliveira, Luciana L Ferreira, Ana Raquel Coelho, Cláudia M Deus, Paulo J Oliveira
Doxorubicin (DOX) is a widely used anticancer drug that could be even more effective if its clinical dosage was not limited because of delayed cardiotoxicity. Beating stem cell-derived cardiomyocytes are a preferred in vitro model to further uncover the mechanisms of DOX-induced cardiotoxicity. Our objective was to use cultured induced-pluripotent stem cell(iPSC)-derived mouse cardiomyocytes (Cor.At) to investigate the effects of DOX on cell and mitochondrial metabolism, as well as on stress responses. Non-proliferating and beating Cor...
April 10, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29652249/clathrin-coat-controls-synaptic-vesicle-acidification-by-blocking-vacuolar-atpase-activity
#13
Zohreh Farsi, Sindhuja Gowrisankaran, Matija Krunic, Burkhard Rammner, Andrew Woehler, Eileen M Lafer, Carsten Mim, Reinhard Jahn, Ira Milosevic
Newly-formed synaptic vesicles (SVs) are rapidly acidified by vacuolar adenosine triphosphatases (vATPases), generating a proton electrochemical gradient that drives neurotransmitter loading. Clathrin-mediated endocytosis is needed for the formation of new SVs, yet it is unclear when endocytosed vesicles acidify and refill at the synapse. Here, we isolated clathrin-coated vesicles (CCVs) from mouse brain to measure their acidification directly at the single vesicle level. We observed that the ATP-induced acidification of CCVs was strikingly reduced in comparison to SVs...
April 13, 2018: ELife
https://www.readbyqxmd.com/read/29651819/biochemical-predictors-of-early-onset-non-alcoholic-fatty-liver-disease-in-young-children-with-obesity
#14
Ju Young Kim, Jinmin Cho, Hye Ran Yang
BACKGROUND: The prevalence of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and their associated risk factors are not well-established in young children with obesity. The purpose of this study was to evaluate the prevalence of early onset NAFLD and identify its biochemical predictors in obese children aged less than 10 years. METHODS: Anthropometric measurements, blood pressure, laboratory tests, and abdominal ultrasonography (USG) were performed in all subjects...
April 16, 2018: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/29644063/metabolic-adaptability-in-hexavalent-chromium-treated-renal-tissue-an-in-vivo-study
#15
Kanu Shil, Sudipta Pal
Background: Hexavalent chromium [Cr(VI)], an environmental pollutant that originates mostly from anthropogenic sources, is a serious threat to human health. After entering into cells, Cr(VI) is capable of producing excessive free radicals and causing tissue damage. The present study aims to reveal the toxic manifestation of Cr(VI) on the metabolic activity of renal tissue. Methods: Male Swiss albino mice were treated orally with potassium dichromate (K2 Cr2 O7 ) at a dose of 10 mg/kg body weight for a period of 30 days...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29642561/%C3%AE-nicotinamide-adenine-dinucleotide-%C3%AE-nad-inhibits-atp-dependent-il-1%C3%AE-release-from-human-monocytic-cells
#16
Sebastian Daniel Hiller, Sarah Heldmann, Katrin Richter, Innokentij Jurastow, Mira Küllmar, Andreas Hecker, Sigrid Wilker, Gabriele Fuchs-Moll, Ivan Manzini, Günther Schmalzing, Wolfgang Kummer, Winfried Padberg, J Michael McIntosh, Jelena Damm, Anna Zakrzewicz, Veronika Grau
While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')- O -(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29627834/effects-of-long-non-coding-rna-linc00963-on-renal-interstitial-fibrosis-and-oxidative-stress-of-rats-with-chronic-renal-failure-via-the-foxo-signaling-pathway
#17
Wen Chen, Lei Zhang, Zhong-Qi Zhou, Yue-Qin Ren, Li-Na Sun, Yu-Lin Man, Zhong-Wei Ma, Zhi-Kui Wang
BACKGROUND/AIMS: Chronic renal failure (CRF) is usually associated with chronic diseases such as congestive heart failure and diabetes mellitus, the prevalence of which is increased with age. This study is designed to investigate the role of long intergenic non-coding RNA (lincRNA) LINC00963 in renal interstitial fibrosis (RIF) and oxidative stress (OS) of CRF via the forkhead box O (FoxO) signaling pathway. METHODS: Microarray data and annotated probe files related to CRF were downloaded by retrieving Gene Expression Omnibus (GEO) database to screen differentially expressed lncRNA...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29625485/atovaquone-impairs-growth-of-aspergillus-and-fusarium-keratitis-isolates-by-modulating-mitochondrial-function-and-zinc-homeostasis
#18
Heather L Clark, Martin S Minns, Yan Sun, Tristan de Jesus, Mahmoud G Ghannoum, Eric Pearlman
Purpose: Aspergillus and Fusarium molds cause blinding corneal infections as a consequence of ocular trauma and in association with contact lens wear. As these fungi require zinc for fungal growth, we examined the effect of atovaquone, a ubiquinone analog that disrupts zinc homeostasis, on fungal growth in vitro and in vivo. Methods: In vitro: Aspergillus and Fusarium germinating conidia were incubated overnight with atovaquone, and hyphal growth was measured by fluorimetry...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29625466/narrow-spectrum-kinase-inhibitors-demonstrate-promise-for-the-treatment-of-dry-eye-disease-and-other-ocular-inflammatory-disorders
#19
Suzanne Hagan, Matthew C T Fyfe, Boatemaa Ofori-Frimpong, Katherine Oliver, Martyn R Foster, Sameer Sirohi, Yemisi Solanke, Michael Doughty, Adele Rowley, Mike Taylor, Steve Webber, Claire A Walshe
Purpose: The purpose of this study is to determine the potential of narrow spectrum kinase inhibitors (NSKIs) to treat inflammatory eye disorders. Methods: Human conjunctival epithelial (HCE) cells were retrieved from subjects via impression cytology. Real-time quantitative PCR (qPCR) was performed on HCE cells to determine gene expression of NSKI kinase targets and proinflammatory cytokines in dry eye disease (DED) patients versus healthy controls. qPCR also assessed p38α expression in hyperosmolar-treated Chang conjunctival epithelial cells...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29625345/toward-an-adverse-outcome-pathway-for-impaired-growth-mitochondrial-dysfunction-impairs-growth-in-early-life-stages-of-the-fathead-minnow-pimephales-promelas
#20
Derek G Bolser, David A Dreier, Erchao Li, Kevin J Kroll, Christopher J Martyniuk, Nancy D Denslow
Chemical contaminants present in the environment can affect mitochondrial bioenergetics in aquatic organisms and can have substantial effects on individual fitness. As early life stages of fish are particularly vulnerable to environmental contaminants, they are ideal models for examining the relationship between impaired mitochondrial bioenergetics (ATP-dependent respiration, basal oxidative respiration) and apical endpoints such as growth. Here, early life stages of the fathead minnow (Pimephales promelas), an ecologically relevant North American species, were used to investigate the relationship between mitochondrial bioenergetics and growth following perturbation with model mitochondrial toxicants 2,4-dinitrophenol and octylamine...
April 3, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
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