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https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#1
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#2
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#3
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28209603/deoxyribonuclease-partially-ameliorates-thioacetamide-induced-hepatorenal-injury
#4
Lenka Vokálová, Lucia Lauková, Jozef Čonka, Veronika Melišková, Veronika Borbélyová, Janka Bábíčková, Ľubomíra Tóthová, Július Hodosy, Barbora Vlková, Peter Celec
Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation exacerbating the liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. In this study the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats were analysed. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals...
February 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28208701/excitotoxins-mitochondrial-and-redox-disturbances-in-multiple-sclerosis
#5
REVIEW
Cecilia Rajda, Dániel Pukoli, Zsuzsanna Bende, Zsófia Majláth, László Vécsei
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207838/viperin-interaction-with-mitochondrial-antiviral-signaling-protein-mavs-limits-viperin-mediated-inhibition-of-the-interferon-response-in-macrophages
#6
Jia Shee Hee, Peter Cresswell
Viperin is an antiviral protein that is upregulated by interferons and by ligands for a variety of innate immune receptors. It possesses diverse capabilities and functions in an array of viral infections. Studies have shown that it appears to be particularly important in defence against RNA viruses, such as West Nile, Dengue, and Chikungunya viruses, although the specific mechanisms involved are not well understood at the molecular level. Here we identify the mitochondrial antiviral signalling protein MAVS as a novel viperin interaction partner, most likely in mitochondria associated membranes, and characterize a more central, overarching role of viperin as a negative regulator of the interferon response, an ability that can be regulated by the viperin-MAVS interaction...
2017: PloS One
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#7
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#8
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28192238/molecular-networks-related-to-the-immune-system-and-mitochondria-are-targets-for-the-pesticide-dieldrin-in-the-zebrafish-danio-rerio-central-nervous-system
#9
Andrew M Cowie, Kathleena I Sarty, Angella Mercer, Jin Koh, Karen A Kidd, Christopher J Martyniuk
: The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides...
February 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28188297/alternative-splicing-in-the-cytochrome-p450-superfamily-expands-protein-diversity-to-augment-gene-function-and-redirect-human-drug-metabolism
#10
Andrew J Annalora, Craig B Marcus, Patrick L Iversen
The human genome encodes 57 cytochrome P450 (CYP) genes whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics and unknown numbers of endogenous compounds including steroids, retinoids and icosinoids. Indeed, CYP genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human CYP transcriptome. This review describes a remarkable diversification of the 57 human CYP genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's CYP proteome...
February 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28186866/toward-postgenomics-ophthalmology-a-proteomic-map-of-the-human-choroid-retinal-pigment-epithelium-tissue
#11
Manjunath Dammalli, Krishna R Murthy, Sneha M Pinto, Kalpana Babu Murthy, Raja Sekhar Nirujogi, Anil K Madugundu, Gourav Dey, Bipin Nair, Harsha Gowda, Thottethodi Subrahmanya Keshava Prasad
Ophthalmology and visual health research have received relatively limited attention from the personalized medicine community, but this trend is rapidly changing. Postgenomics technologies such as proteomics are being utilized to establish a baseline biological variation map of the human eye and related tissues. In this context, the choroid is the vascular layer situated between the outer sclera and the inner retina. The choroidal circulation serves the photoreceptors and retinal pigment epithelium (RPE). The RPE is a layer of cuboidal epithelial cells adjacent to the neurosensory retina and maintains the outer limit of the blood-retina barrier...
February 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28183981/a-switch-from-canonical-to-noncanonical-autophagy-shapes-b-cell-responses
#12
Nuria Martinez-Martin, Paula Maldonado, Francesca Gasparrini, Bruno Frederico, Shweta Aggarwal, Mauro Gaya, Carlson Tsui, Marianne Burbage, Selina Jessica Keppler, Beatriz Montaner, Harold B J Jefferies, Usha Nair, Yan G Zhao, Marie-Charlotte Domart, Lucy Collinson, Andreas Bruckbauer, Sharon A Tooze, Facundo D Batista
Autophagy is important in a variety of cellular and pathophysiological situations; however, its role in immune responses remains elusive. Here, we show that among B cells, germinal center (GC) cells exhibited the highest rate of autophagy during viral infection. In contrast to mechanistic target of rapamycin complex 1-dependent canonical autophagy, GC B cell autophagy occurred predominantly through a noncanonical pathway. B cell stimulation was sufficient to down-regulate canonical autophagy transiently while triggering noncanonical autophagy...
February 10, 2017: Science
https://www.readbyqxmd.com/read/28181526/no-effect-of-mitochondrial-genotype-on-reproductive-plasticity-following-exposure-to-a-non-infectious-pathogen-challenge-in-female-or-male-drosophila
#13
M Nystrand, E J Cassidy, D K Dowling
Mitochondrial genetic variation shapes the expression of life-history traits associated with reproduction, development and survival, and has also been associated with the prevalence and progression of infectious bacteria and viruses in humans. The breadth of these effects on multifaceted components of health, and their link to disease susceptibility, led us to test whether variation across mitochondrial haplotypes affected reproductive success following an immune challenge in the form of a non-infectious pathogen...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181350/no-evidence-of-a-role-for-mitochondrial-complex-i-in-helicobacter-pylori-pathogenesis
#14
Garrett Z Ng, Bi-Xia Ke, Adrienne Laskowski, David R Thorburn, Philip Sutton
BACKGROUND: Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis...
February 9, 2017: Helicobacter
https://www.readbyqxmd.com/read/28179442/t-helper-cell-type-2-th2-and-non-th2-molecular-phenotypes-of-asthma-using-sputum-transcriptomics-in-u-biopred
#15
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Iaonnis Pandis, Ana Sousa, Julie Corfield, Ratko Djukanovic, Rene Lutter, Peter J Sterk, Charles Auffray, Yike Guo, Ian M Adcock, Kian Fan Chung
Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects.After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets.We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R, CCR3 and TSLPR), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function)...
February 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28179110/oxidized-and-original-article-degraded-mitochondrial-polynucleotides-demps-especially-rna-are-potent-immunogenic-regulators-in-primary-mouse-macrophages
#16
Abhinav R Saxena, Linda Y Gao, Shachi Srivatsa, Elizabeth Z Bobersky, Sivakumar Periasamy, Danielle T Hunt, Kyle E Altman, Dana R Crawford
Certain mitochondrial components can act as damage-associated molecular patterns (DAMPs) or danger signals, triggering a proinflammatory response in target (usually immune) cells. We previously reported the selective degradation of mitochondrial DNA and RNA in response to cellular oxidative stress, and the immunogenic effect of this DNA in primary mouse astrocytes. Here, we extend these studies to assess the immunogenic role of both mitochondrial DNA and RNA isolated from hydrogen peroxide (HP) treated HA1 cells (designated "DeMPs" for degraded mitochondrial polynucleotides) using mouse bone marrow derived macrophages (BMDMs), a conventional immune cell type...
February 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28178278/advances-in-the-quantification-of-mitochondrial-function-in-primary-human-immune-cells-through-extracellular-flux-analysis
#17
Dequina Nicholas, Elizabeth A Proctor, Forum M Raval, Blanche C Ip, Chloe Habib, Eleni Ritou, Tom N Grammatopoulos, Devin Steenkamp, Hans Dooms, Caroline M Apovian, Douglas A Lauffenburger, Barbara S Nikolajczyk
Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks...
2017: PloS One
https://www.readbyqxmd.com/read/28174739/increased-mitochondrial-genetic-diversity-in-persons-infected-with-hepatitis-c-virus
#18
David S Campo, Ha-Jung Roh, Brian L Pearlman, Daniel S Fierer, Sumathi Ramachandran, Gilberto Vaughan, Andrew Hinds, Zoya Dimitrova, Pavel Skums, Yury Khudyakov
BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28162008/clinical-implications-of-understanding-the-association-between-oxidative-stress-and-pediatric-nafld
#19
Jake P Mann, Massimiliano Raponi, Valerio Nobili
Oxidative stress is central to the pathogenesis of non-alcoholic steatohepatitis. The reactive oxygen species (ROS) that characterise oxidative stress are generated in several cellular sites and their production is influence by multi-organ interactions. Areas covered: Mitochondrial dysfunction is the main source of ROS in fatty liver and is closely related to endoplasmic reticulum stress. Both are caused by lipotoxicity and together these three factors form a cycle of progressive organelle damage, resulting in sterile inflammation and apoptosis...
February 6, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28155620/nlrp3-inhibitors-as-potential-therapeutic-agents-for-treatment-of-inflammatory-bowel-disease
#20
Agampodi Promoda Perera, Dale Kunde, Rajaraman Eri
BACKGROUND: Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised by chronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis or Crohn's disease and increases the risk of developing colorectal cancer. METHODS: Here, we have reviewed current treatment regimen for IBD utilising anti-inflammatory drugs, immune system suppressors and antibiotics or a combination of these. However, these therapeutics lead to a number of adverse effects, remission or significant non-responsiveness creating an urgent need to develop potent drugs with novel mechanisms of action for IBD...
February 1, 2017: Current Pharmaceutical Design
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