674 results on '"Hogg, N."'
Search Results
152. Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3.
- Author
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Myones, B L, primary, Dalzell, J G, additional, Hogg, N, additional, and Ross, G D, additional
- Published
- 1988
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153. Activity of Two Types of Fc Receptors, FcgammaRI and FcgammaRII, in Human Monocyte Cytotoxicity to Sensitized Erythrocytes
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WINKEL, J. G. J., primary, BOONEN, G. J. J. C., additional, JANSSEN, P. L. W., additional, VLUG, A., additional, HOGG, N., additional, and TAX, W. J. M., additional
- Published
- 1989
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154. Identification of IL 2R+ T cells and macrophages within rejecting rat cardiac allografts, and comparison of the effects of treatment with anti-IL 2R monoclonal antibody or cyclosporin.
- Author
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Hancock, W W, primary, Lord, R H, additional, Colby, A J, additional, Diamantstein, T, additional, Rickles, F R, additional, Dijkstra, C, additional, Hogg, N, additional, and Tilney, N L, additional
- Published
- 1987
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155. Design and operation of a long-duration mooring for ocean observations
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Frye, D., primary, Hogg, N., additional, and Wunsch, C., additional
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- View/download PDF
156. What is hindering the adoption of new annual pasture legumes? Extension requirements to over come these barriers.
- Author
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Hogg, N. and Davis, J. K.
- Subjects
FARM management ,PASTURES ,LEGUMES ,SUBTERRANEAN clover ,AGRICULTURE - Abstract
Farmers and consultants were surveyed to identify current level of adoption and constraints to adoption of new annual pasture legumes in the mixed farming zone of Western Australia. Subterranean clover is the most widely grown annual pasture legume and promoted by all the consultants. French and yellow serradellas and biserrula are recommended by up to 40% of consultants and grown by 20 to 30% of growers: far less than sub clover. Adoption is considered to be constrained by the 'cost of establishment' along with unpredictable/unreliable seasonal rainfall. The consultants suggested there is potential for wider adoption of the new pasture legumes across the mixed farming zone of Western Australia. They regard the information produced from the Department of Agriculture and Food WA as reliable, but want more information. Extension resources need to enable farmers and their consultants to estimate benefits of legumes in systems in which livestock are absent or less important. Key learning's: • In order to successfully integrate new annual pasture legumes into farming systems, growers and consultants need to be provided with information on economic benefits as well as technical detail relating to production and management. • The main barriers to adoption of new annual pasture legumes are the perceived cost of establishment and unreliable production in variable environments. • Subterranean clover is the most widely grown and recommended pasture species and a useful benchmark against which to compare the performance of the new species. [ABSTRACT FROM AUTHOR]
- Published
- 2009
157. The use of nasal retainers in primary and secondary functional cheilorhinoplasty.
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Precious, D. and Hogg, N.
- Published
- 2006
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158. Design and operation of a long-duration mooring for ocean observations.
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Frye, D., Hogg, N., and Wunsch, C.
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- 2002
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159. On the transport of the Gulf Stream between Cape Hatteras and the Grand Banks
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Hogg, N. G.
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- 1992
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160. Tips and timesavers.
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Davis C, Langlinais J, Miles A, Mitchell L, Hogg N, Eggen MK, Locsin RGR, Goodhart S, and Purner R
- Published
- 1980
161. THE DISTRIBUTION OF CROSS-LINKED FIBRIN IN HUMAN LUNG CARCINOMA PARALLELS THAT OF ACTIVATED HOST MONONUCLEAR LEUKOCYTES: IMMUNO-HISTOLOGIC STUDIES WITH MONOCLONAL ANTIBODIES
- Author
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Rickles, F R, Hancock, W W, Kobzik, K, Hogg, N, and O’Hara, C
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- 1987
- Full Text
- View/download PDF
162. Factor-induced differentiation and activation of macrophages
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HOGG, N
- Published
- 1986
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163. The structure and function of Fc receptors
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Hogg, N
- Published
- 1988
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164. The leukocyte integrins
- Author
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HOGG, N
- Published
- 1989
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165. Inhibition of low-density lipoprotein oxidation by nitric oxide: Potential role in atherogenesis (FEBS 13240)
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Hogg, N., Kalyanaraman, B., Joseph, J., and Struck, A.
- Published
- 1993
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166. Monoclonal antibody with specificity for monocytes and neurons
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Hogg, N
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- 1981
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167. Roll, roll, roll your leucocyte gently down the vein.
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Hogg, N
- Published
- 1992
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168. Structure and function of adhesion receptors in leukocyte trafficking
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Hogg, N
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- 1995
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169. Nitric oxide donor compounds inhibit the toxicity of oxidized low-density lipoprotein to endothelial cells
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Struck, A. T., Hogg, N., Thomas, J. P., and Kalyanaraman, B.
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- 1995
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170. Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor
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Graham, A., Hogg, N., Kalyamaraman, B., and O'Leary, V.
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- 1993
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171. Phosphatidylethanolamine is progressively exposed in RBCs during storage.
- Author
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Larson, M. C., Karafin, M. S., Hillery, C. A., and Hogg, N.
- Subjects
- *
PHOSPHATIDYLETHANOLAMINES , *ERYTHROCYTES , *CELL preservation , *BLOOD transfusion , *HEMOGLOBINS , *FLOW cytometry , *PHYSIOLOGY - Abstract
SUMMARY Background It is well established that as a blood unit ages, fewer of the unit's red blood cells (RBCs) remain in circulation post-transfusion. The mechanism for clearance is not well defined. Phosphatidylethanolamine (PE) is a phospholipid that is primarily found on the inner leaflet of healthy cells, and is an important ligand for phagocytosis of dead cells when exposed. Objectives The objective of the present study was to measure the change in PE exposure in donor RBCs over increasing storage ages using the novel PE-specific probe, duramycin. Methods Five adsol (AS-1) preserved RBC units were sampled weekly for 6 weeks and were labelled with duramycin. The percentage of PE exposed on red cells in each sample was determined using flow cytometry. Surface phosphatidylserine (PS) was evaluated for comparison. Results We found that RBCs in AS-preserved donor units increasingly exposed PE, from less than 1% in freshly processed RBCs, to nearly 20% at 42 days of storage and correlated with increased relative vesiculation or microparticle concentration and release of cell-free haemoglobin. By comparison, only 5% of cells exposed PS at 42 days. Conclusion We conclude that exposure of PE in the RBC outer membrane was higher than that of PS during 42 days of storage and correlated significantly with increased vesiculation and release of haemoglobin. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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172. Integrins and ICAM-1 in Immune Responses
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Hogg, N. and Hogg, N.
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- Immune response, Cell receptors, Cell adhesion molecules
- Published
- 1991
173. ECG dots and regional blocks.
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Webb, L, Trenfield, S, and Hogg, N
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- 2001
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174. The effects of free radicals on cytochrome [formula omitted] oxidase vesicals(covs)
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Hogg, N., Wilson, M.T., and Darley-Usmar, V.
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- 1991
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175. How leukocytes use integrins to adhere to targets
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Hogg, N.
- Published
- 1998
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176. Imaging thrombus with radiolabelled monoclonal antibody to platelets.
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Peters, A.M., Lavender, J.P., Needham, S.G., Loutfi, I., Snook, D., Epenetos, A.A., Lumley, P., Keery, R.J., and Hogg, N.
- Subjects
- *
RADIOLOGY , *MONOCLONAL antibodies ,BLOOD platelet examination - Abstract
Evaluates the method of imaging thrombus with radiolabelled monoclonal antibody to platelets. Lack of immunoreactivity impairment; Absence of platelet activation after intravenous P256 and radiolabelling of platelets; Potential of imaging thrombus as a simple and non-invasive approach to the diagnosis of thrombosis.
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- 1986
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177. Train no. 99 to Sippewissett farm
- Author
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Zenk, Walter, Luyten, J., and Hogg, N.
- Published
- 1992
178. β-Cell-selective regulation of gene expression by nitric oxide.
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Naatz A, Yeo CT, Hogg N, and Corbett JA
- Subjects
- Animals, Mice, Transcription Factors metabolism, Transcription Factors genetics, Transcription Factor CHOP metabolism, Transcription Factor CHOP genetics, HSP70 Heat-Shock Proteins metabolism, HSP70 Heat-Shock Proteins genetics, Heme Oxygenase (Decyclizing) metabolism, Heme Oxygenase (Decyclizing) genetics, Cell Cycle Proteins metabolism, Cell Cycle Proteins genetics, Insulin metabolism, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins genetics, Rats, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Membrane Proteins, Heme Oxygenase-1, Nitric Oxide metabolism, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells drug effects, Nitric Oxide Synthase Type II metabolism, Nitric Oxide Synthase Type II genetics, Gene Expression Regulation drug effects, Apoptosis Regulatory Proteins metabolism, Apoptosis Regulatory Proteins genetics
- Abstract
Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It is through the inhibition of mitochondrial oxidative metabolism, specifically aconitase and complex 4 of the electron transport chain, that nitric oxide inhibits insulin secretion. Nitric oxide also attenuates protein synthesis, induces DNA damage, activates DNA repair pathways, and stimulates stress responses (unfolded protein and heat shock) in β-cells. In this report, the time- and concentration-dependent effects of nitric oxide on the expression of six genes known to participate in the response of β-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and Ppargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates β-cell gene expression in a narrow concentration range of ∼0.5-1 µM or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in β-cells, and this is associated with the inhibition of mitochondrial oxidative metabolism. This narrow concentration range of responses is β-cell selective, as the actions of nitric oxide in non-β-cells (α-cells, mouse embryonic fibroblasts, and macrophages) are concentration dependent. Our findings suggest that β-cells respond to a narrow concentration range of nitric oxide that is consistent with the levels produced following iNOS induction, and that these concentration-dependent actions are selective for insulin-containing cells.
- Published
- 2024
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179. Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease.
- Author
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Rarick KR, Li K, Teng RJ, Jing X, Martin DP, Xu H, Jones DW, Hogg N, Hillery CA, Garcia G, Day BW, Naylor S, and Pritchard KA Jr
- Subjects
- Humans, Animals, Mice, Endothelial Cells metabolism, Inflammation, Lung Injury etiology, HMGB1 Protein genetics, Anemia, Sickle Cell drug therapy, Anemia, Sickle Cell genetics, Lung Diseases, Vascular Diseases etiology, Benzamides, Pyrroles
- Abstract
Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice. SS mice were treated with either phosphate-buffered saline (PBS), hE-HMGB1-BP, an hE dual-domain peptide that binds and removes HMGB1 from the circulation via the liver, 1-[4-(aminocarbonyl)-2-methylphenyl]-5-[4-(1H-imidazol-1-yl)phenyl]-1H-pyrrole-2-propanoic acid (N6022) or N-acetyl-lysyltyrosylcysteine amide (KYC) for three weeks. Human umbilical vein endothelial cells (HUVEC) were treated with recombinant HMGB1 (r-HMGB1), which increases S-nitrosoglutathione reductase (GSNOR) expression by ∼80%, demonstrating a direct effect of HMGB1 to increase GSNOR. Treatment of SS mice with hE-HMGB1-BP reduced plasma HMGB1 in SS mice to control levels and reduced GSNOR expression in facialis arteries isolated from SS mice by ∼20%. These changes were associated with improved endothelial-dependent vasodilation. Treatment of SS mice with N6022 also improved vasodilation in SS mice suggesting that targeting GSNOR also improves vasodilation. SCD decreased protein nitrosothiols (SNOs) and radial alveolar counts (RAC) and increased GSNOR expression and mean linear intercepts (MLI) in lungs from SS mice. The marked changes in pulmonary morphometrics and GSNOR expression throughout the lung parenchyma in SS mice were improved by treating with either hE-HMGB1-BP or KYC. These data demonstrate that murine SCD induces vasculopathy and chronic lung disease by an HMGB1- and GSNOR-dependent mechanism and suggest that HMGB1 and GSNOR might be effective therapeutic targets for reducing vasculopathy and chronic lung disease in humans with SCD., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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180. N-acetyl-lysyltyrosylcysteine amide, a novel systems pharmacology agent, reduces bronchopulmonary dysplasia in hyperoxic neonatal rat pups.
- Author
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Teng RJ, Jing X, Martin DP, Hogg N, Haefke A, Konduri GG, Day BW, Naylor S, and Pritchard KA Jr
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- Amides, Animals, Animals, Newborn, Humans, Hydrogen Peroxide, Infant, Newborn, Kelch-Like ECH-Associated Protein 1 metabolism, Lung metabolism, NF-E2-Related Factor 2 metabolism, Rats, Bronchopulmonary Dysplasia, Hyperoxia
- Abstract
Bronchopulmonary dysplasia (BPD) is caused primarily by oxidative stress and inflammation. To induce BPD, neonatal rat pups were raised in hyperoxic (>90% O
2 ) environments from day one (P1) until day ten (P10) and treated with N-acetyl-lysyltyrosylcysteine amide (KYC). In vivo studies showed that KYC improved lung complexity, reduced myeloperoxidase (MPO) positive (+) myeloid cell counts, MPO protein, chlorotyrosine formation, increased endothelial cell CD31 expression, decreased 8-OH-dG and Cox-1/Cox-2, HMGB1, RAGE, TLR4, increased weight gain and improved survival in hyperoxic pups. EPR studies confirmed that MPO reaction mixtures oxidized KYC to a KYC thiyl radical. Adding recombinant HMGB1 to the MPO reaction mixture containing KYC resulted in KYC thiylation of HMGB1. In rat lung microvascular endothelial cell (RLMVEC) cultures, KYC thiylation of RLMVEC proteins was increased the most in RLMVEC cultures treated with MPO + H2 O2 , followed by H2 O2 , and then KYC alone. KYC treatment of hyperoxic pups decreased total HMGB1 in lung lysates, increased KYC thiylation of HMGB1, terminal HMGB1 thiol oxidation, decreased HMGB1 association with TLR4 and RAGE, and shifted HMGB1 in lung lysates from a non-acetylated to a lysyl-acetylated isoform, suggesting that KYC reduced lung cell death and that recruited immune cells had become the primary source of HMGB1 released into the hyperoxic lungs. MPO-dependent and independent KYC-thiylation of Keap1 were both increased in RLMVEC cultures. Treating hyperoxic pups with KYC increased KYC thiylation and S-glutathionylation of Keap1, and Nrf2 activation. These data suggest that KYC is a novel system pharmacological agent that exploits MPO to inhibit toxic oxidant production and is oxidized into a thiyl radical that inactivates HMGB1, activates Nrf2, and increases antioxidant enzyme expression to improve lung complexity and reduce BPD in hyperoxic rat pups., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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181. Centrifugation Removes a Population of Large Vesicles, or "Macroparticles," Intermediate in Size to RBCs and Microvesicles.
- Author
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Larson MC, Hogg N, and Hillery CA
- Subjects
- Anemia, Hemolytic genetics, Anemia, Hemolytic pathology, Animals, Cell Lineage genetics, Erythrocyte Count, Hemoglobins genetics, Humans, Mice, Anemia, Hemolytic blood, Cell-Derived Microparticles genetics, Centrifugation, Erythrocytes cytology
- Abstract
Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 µm size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.
- Published
- 2021
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182. Nitric Oxide Circumvents Virus-Mediated Metabolic Regulation during Human Cytomegalovirus Infection.
- Author
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Mokry RL, Schumacher ML, Hogg N, and Terhune SS
- Subjects
- Adenosine Triphosphate metabolism, Cell Line, Citric Acid Cycle, Cytomegalovirus genetics, Cytomegalovirus Infections immunology, Glutamine metabolism, Glutathione metabolism, Host-Pathogen Interactions, Humans, Mitochondria metabolism, Nitric Oxide immunology, Virus Replication, Cytomegalovirus physiology, Cytomegalovirus Infections metabolism, Cytomegalovirus Infections virology, Nitric Oxide metabolism
- Abstract
Nitric oxide is a versatile and critical effector molecule that can modulate many cellular functions. Although recognized as a regulator of infections, the inhibitory mechanism of nitric oxide against human cytomegalovirus (HCMV) replication remains elusive. We demonstrate that nitric oxide attenuates viral replication by interfering with HCMV-mediated modulation of several cellular processes. Nitric oxide exposure reduced HCMV genome synthesis and infectious viral progeny with cell-type-dependent differences observed. Mitochondrial respiration was severely reduced in both uninfected and HCMV-infected cells during exposure with little impact on ATP levels indicating changes in cellular metabolism. Metabolomics identified significantly altered small molecules in multiple pathways during nitric oxide exposure including nucleotide biosynthesis, tricarboxylic acid (TCA) cycle, and glutamine metabolism. Glutathione metabolites were increased coinciding with a reduction in the glutathione precursor glutamine. This shift was accompanied by increased antioxidant enzymes. Glutamine deprivation mimicked defects in HCMV replication and mitochondrial respiration observed during nitric oxide exposure. These data suggest that nitric oxide limits glutaminolysis by shuttling glutamine to glutathione synthesis. In addition, lipid intermediates were severely altered, which likely contributes to the observed increase in defective viral particles. Nitric oxide disrupts multiple cellular processes, and we had limited success in rescuing replication defects by supplementing with metabolic intermediates. Our studies indicate that nitric oxide attenuation of HCMV is multifactorial with interference in viral manipulation of cellular metabolism playing a central role. IMPORTANCE Human cytomegalovirus is a prevalent pathogen that can cause serious disease in patients with compromised immune systems, including transplant patients and during congenital infection. HCMV lytic replication likely occurs in localized sites of infection with immune cells infiltrating and releasing nitric oxide with other effector molecules. This nonspecific immune response results in both uninfected and infected cells exposed to high levels of nitric oxide. The absence of nitric oxide synthase has been associated with lethal HCMV infection. We demonstrate that nitric oxide inhibition of HCMV replication is multifactorial and cell type dependent. Our results indicate that nitric oxide controls replication by interfering with viral modulation of cellular metabolism while also affecting proliferation and mitochondrial respiration of neighboring uninfected cells. These studies identify the mechanism and contribution of nitric oxide during immune control of HCMV infection and provide insight into its role in other viral infections., (Copyright © 2020 Mokry et al.)
- Published
- 2020
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183. Myoglobin promotes nitrite-dependent mitochondrial S-nitrosation to mediate cytoprotection after hypoxia/reoxygenation.
- Author
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Quesnelle K, Guimaraes DA, Rao K, Singh AB, Wang Y, Hogg N, and Shiva S
- Subjects
- Animals, CHO Cells, Cell Hypoxia physiology, Cricetulus, Cysteine chemistry, Electron Transport Complex I chemistry, Electron Transport Complex I metabolism, Humans, Mitochondrial Proteins chemistry, Mitochondrial Proteins metabolism, Nitrosation, Cytoprotection physiology, Mitochondria metabolism, Myoglobin metabolism, Nitrite Reductases metabolism, Nitrites metabolism
- Abstract
It is well established that myoglobin supports mitochondrial respiration through the storage and transport of oxygen as well as through the scavenging of nitric oxide. However, during ischemia/reperfusion (I/R), myoglobin and mitochondria both propagate myocardial injury through the production of oxidants. Nitrite, an endogenous signaling molecule and dietary constituent, mediates potent cardioprotection after I/R and this effect relies on its interaction with both myoglobin and mitochondria. While independent mechanistic studies have demonstrated that nitrite-mediated cardioprotection requires the presence of myoglobin and the post-translational S-nitrosation of critical cysteine residues on mitochondrial complex I, it is unclear whether myoglobin directly catalyzes the S-nitrosation of complex I or whether mitochondrial-dependent nitrite reductase activity contributes to S-nitrosation. Herein, using purified myoglobin and isolated mitochondria, we characterize and directly compare the nitrite reductase activities of mitochondria and myoglobin and assess their contribution to mitochondrial S-nitrosation. We demonstrate that myoglobin is a significantly more efficient nitrite reductase than isolated mitochondria. Further, deoxygenated myoglobin catalyzes the nitrite-dependent S-nitrosation of mitochondrial proteins. This reaction is enhanced in the presence of oxidized (Fe
3+ ) myoglobin and not significantly affected by inhibitors of mitochondrial respiration. Using a Chinese Hamster Ovary cell model stably transfected with human myoglobin, we show that both myoglobin and mitochondrial complex I expression are required for nitrite-dependent attenuation of cell death after anoxia/reoxygenation. These data expand the understanding of myoglobin's role both as a nitrite reductase to a mediator of S-nitrosation and as a regulator of mitochondrial function, and have implications for nitrite-mediated cardioprotection after I/R., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
184. Peroxiredoxin 1 plays a primary role in protecting pancreatic β-cells from hydrogen peroxide and peroxynitrite.
- Author
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Stancill JS, Happ JT, Broniowska KA, Hogg N, and Corbett JA
- Subjects
- Animals, Cell Death, Cell Line, Tumor, Cytoplasm enzymology, Cytoprotection, Enzyme Inhibitors pharmacology, Insulin-Secreting Cells enzymology, Insulin-Secreting Cells pathology, Male, Peroxiredoxins antagonists & inhibitors, Peroxiredoxins genetics, Quinoxalines pharmacology, RNA Interference, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Rats, Sprague-Dawley, Signal Transduction, Thioredoxin Reductase 1 metabolism, DNA Damage, Hydrogen Peroxide toxicity, Insulin-Secreting Cells drug effects, Oxidative Stress drug effects, Peroxiredoxins metabolism, Peroxynitrous Acid toxicity
- Abstract
Both reactive nitrogen and oxygen species (RNS and ROS), such as nitric oxide, peroxynitrite, and hydrogen peroxide, have been implicated as mediators of pancreatic β-cell damage during the pathogenesis of autoimmune diabetes. While β-cells are thought to be vulnerable to oxidative damage due to reportedly low levels of antioxidant enzymes, such as catalase and glutathione peroxidase, we have shown that they use thioredoxin reductase to detoxify hydrogen peroxide. Thioredoxin reductase is an enzyme that participates in the peroxiredoxin antioxidant cycle. Peroxiredoxins are expressed in β-cells and, when overexpressed, protect against oxidative stress, but the endogenous roles of peroxiredoxins in the protection of β-cells from oxidative damage are unclear. Here, using either glucose oxidase or menadione to continuously deliver hydrogen peroxide, or the combination of dipropylenetriamine NONOate and menadione to continuously deliver peroxynitrite, we tested the hypothesis that β-cells use peroxiredoxins to detoxify both of these reactive species. Either pharmacological peroxiredoxin inhibition with conoidin A or specific depletion of cytoplasmic peroxiredoxin 1 ( Prdx1 ) using siRNAs sensitizes INS 832/13 cells and rat islets to DNA damage and death induced by hydrogen peroxide or peroxynitrite. Interestingly, depletion of peroxiredoxin 2 ( Prdx2 ) had no effect. Together, these results suggest that β-cells use cytoplasmic Prdx1 as a primary defense mechanism against both ROS and RNS.
- Published
- 2020
- Full Text
- View/download PDF
185. The Role of Metabolic Flexibility in the Regulation of the DNA Damage Response by Nitric Oxide.
- Author
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Oleson BJ, Broniowska KA, Yeo CT, Flancher M, Naatz A, Hogg N, Tarakanova VL, and Corbett JA
- Subjects
- Adenosine Triphosphate metabolism, Animals, Cell Line, Cell Respiration drug effects, Cell Survival drug effects, DNA Damage, Hep G2 Cells, Humans, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Male, Mice, Mitochondria drug effects, Mitochondria metabolism, NAD metabolism, Rats, Rats, Sprague-Dawley, DNA Repair drug effects, Glycolysis drug effects, Insulin-Secreting Cells cytology, Nitric Oxide pharmacology
- Abstract
In this report, we show that nitric oxide suppresses DNA damage response (DDR) signaling in the pancreatic β-cell line INS 832/13 and rat islets by inhibiting intermediary metabolism. Nitric oxide is known to inhibit complex IV of the electron transport chain and aconitase of the Krebs cycle. Non-β cells compensate by increasing glycolytic metabolism to maintain ATP levels; however, β cells lack this metabolic flexibility, resulting in a nitric oxide-dependent decrease in ATP and NAD
+ Like nitric oxide, mitochondrial toxins inhibit DDR signaling in β cells by a mechanism that is associated with a decrease in ATP. Non-β cells compensate for the effects of mitochondrial toxins with an adaptive shift to glycolytic ATP generation that allows for DDR signaling. Forcing non-β cells to derive ATP via mitochondrial respiration (replacing glucose with galactose in the medium) and glucose deprivation sensitizes these cells to nitric oxide-mediated inhibition of DDR signaling. These findings indicate that metabolic flexibility is necessary to maintain DDR signaling under conditions in which mitochondrial oxidative metabolism is inhibited and support the inhibition of oxidative metabolism (decreased ATP) as one protective mechanism by which nitric oxide attenuates DDR-dependent β-cell apoptosis., (Copyright © 2019 American Society for Microbiology.)- Published
- 2019
- Full Text
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186. Associations between Health Assessment Questionnaire Disability Index and physical performance in rheumatoid arthritis and osteoarthritis.
- Author
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Douglas-Withers J, McCulloch K, Waters D, Parker K, Hogg N, Mitsuhashi T, Treharne GJ, Abbott JH, and Stebbings S
- Subjects
- Actigraphy instrumentation, Aged, Arthritis, Rheumatoid physiopathology, Female, Fitness Trackers, Hand Strength, Health Status, Humans, Male, Middle Aged, Muscle Strength Dynamometer, Osteoarthritis, Hip physiopathology, Osteoarthritis, Knee physiopathology, Predictive Value of Tests, Time Factors, Arthritis, Rheumatoid diagnosis, Disability Evaluation, Osteoarthritis, Hip diagnosis, Osteoarthritis, Knee diagnosis, Patient Reported Outcome Measures
- Abstract
Objectives: To investigate whether the Health Assessment Questionnaire Disability Index (HAQ-DI) reflects objective measures of physical function in people with osteoarthritis (OA) and rheumatoid arthritis (RA)., Methods: In total, 139 people, 71 with RA fulfilling the American College of Rheumatology (ACR) criteria (1987) and 68 with OA fulfilling ACR criteria for OA of the hip or knee, completed the HAQ-DI. Physical function was assessed using Timed Up and Go (TUG), 30 seconds Sit to Stand (STS), grip strength dynamometry and pedometer steps over 7 days., Results: The strongest association with HAQ-DI was with the TUG (R
2 of 0.671 and 0.512 in RA and OA groups, respectively). HAQ-DI and STS showed a non-linear association in both groups with R2 of 0.380 in RA and 0.359 in OA. A strong association was found between HAQ-DI and grip strength in the OA group (R2 = 0.681), whereas the RA group showed a moderate association (R2 = 0.285). There was a strong association between the HAQ-DI and pedometer measures in RA (R2 = 0.562), although this association was weak in OA (R2 = 0.156)., Conclusion: The HAQ-DI has a strong association with the TUG in both RA and OA. There was variable association between the HAQ-DI and other physical performance measures, as well as differences between the RA and OA cohorts. In order to form a full and accurate clinical picture, health professionals should perform both subjective patient-reported outcome measures and objective physical performance measures of disability., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)- Published
- 2019
- Full Text
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187. Corrigendum to "Red/near infrared light stimulates release of an endothelium dependent vasodilator and rescues vascular dysfunction in a diabetes model" [Free Radic. Biol. Med. 113:157-164].
- Author
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Keszler A, Lindemer B, Weihrauch D, Jones D, Hogg N, and Lohr NL
- Published
- 2019
- Full Text
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188. Ascorbate attenuates red light mediated vasodilation: Potential role of S-nitrosothiols.
- Author
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Keszler A, Lindemer B, Hogg N, and Lohr NL
- Subjects
- Acetylcholine pharmacology, Animals, Arteries drug effects, Arteries metabolism, Arteries radiation effects, Mice, Models, Biological, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Ascorbic Acid pharmacology, Light, S-Nitrosothiols pharmacology, Vasodilation drug effects, Vasodilation radiation effects, Vasodilator Agents pharmacology
- Abstract
There is significant therapeutic advantage of nitric oxide synthase (NOS) independent nitric oxide (NO) production in maladies where endothelium, and thereby NOS, is dysfunctional. Electromagnetic radiation in the red and near infrared region has been shown to stimulate NOS-independent but NO-dependent vasodilation, and thereby has significant therapeutic potential. We have recently shown that red light induces acute vasodilatation in the pre-constricted murine facial artery via the release of an endothelium derived substance. In this study we have investigated the mechanism of vasodilatation and conclude that 670 nm light stimulates vasodilator release from an endothelial store, and that this vasodilator has the characteristics of an S-nitrosothiol (RSNO). This study shows that 670 nm irradiation can be used as a targeted and non-invasive means to release biologically relevant amounts of vasodilator from endothelial stores. This raises the possibility that these stores can be pharmacologically built-up in pathological situations to improve the efficacy of red light treatment. This strategy may overcome eNOS dysfunction in peripheral vascular pathologies for the improvement of vascular health., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2019
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189. Rust never sleeps: The continuing story of the Iron Bolt.
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van der Vliet A, Dick TP, Aust SD, Koppenol WH, Ursini F, Kettle AJ, Beckman JS, O'Donnell V, Darley-Usmar V, Lancaster J Jr, Hogg N, Davies KJA, Forman HJ, and Janssen-Heininger YMW
- Subjects
- Humans, Awards and Prizes, Free Radicals
- Abstract
Since 1981, Gordon Research Conferences have been held on the topic of Oxygen Radicals on a biennial basis, to highlight and discuss the latest cutting edge research in this area. Since the first meeting, one special feature of this conference has been the awarding of the so-called Iron Bolt, an award that started in jest but has gained increasing reputation over the years. Since no written documentation exists for this Iron Bolt award, this perspective serves to overview the history of this unusual award, and highlights various experiences of previous winners of this "prestigious" award and other interesting anecdotes., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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190. Wavelength-dependence of vasodilation and NO release from S-nitrosothiols and dinitrosyl iron complexes by far red/near infrared light.
- Author
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Keszler A, Lindemer B, Hogg N, Weihrauch D, and Lohr NL
- Subjects
- Animals, Arteries radiation effects, Infrared Rays, Light, Mice, Inbred C57BL, Vasodilation radiation effects, Arteries drug effects, Iron pharmacology, Nitric Oxide metabolism, Nitric Oxide Donors pharmacology, Nitrogen Oxides pharmacology, S-Nitrosothiols pharmacology, Vasodilation drug effects
- Abstract
Far red/near infrared (R/NIR) energy is a novel therapy, but its mechanism of action is poorly characterized. Cytochrome c oxidase (Cco) of the mitochondrial electron transport chain is considered the primary photoacceptor for R/NIR to photolyze a putative heme nitrosyl in Cco to liberate free nitric oxide (NO). We previously observed R/NIR light directly liberates NO from nitrosylated hemoglobin and myoglobin, and recently suggested S-nitrosothiols (RSNO) and dinitrosyl iron complexes (DNIC) may be primary sources of R/NIR-mediated NO. Here we indicate R/NIR light exposure induces wavelength dependent dilation of murine facial artery, with longer wavelengths (740, and 830 nm) exhibiting reduced potency when compared to 670 nm. R/NIR also stimulated NO release from pure solutions of low molecular weight RSNO (GSNO and SNAP) and glutathione dinitrosyl iron complex (GSH-DNIC) in a power- and wavelength-dependent manner, with the greatest effect at 670 nm. NO release from SNAP using 670 was nearly ten-fold more than GSNO or GSH-DNIC, with no substantial difference in NO production at 740 nm and 830 nm. Thermal effects of irradiation on vasodilation or NO release from S-nitrosothiols and DNIC was minimal. Our results suggest 670 nm is the optimal wavelength for R/NIR treatment of certain vascular-related diseases., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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- View/download PDF
191. Red/near infrared light stimulates release of an endothelium dependent vasodilator and rescues vascular dysfunction in a diabetes model.
- Author
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Keszler A, Lindemer B, Weihrauch D, Jones D, Hogg N, and Lohr NL
- Subjects
- Animals, Diabetes Mellitus, Experimental enzymology, Endothelium, Vascular enzymology, Endothelium, Vascular radiation effects, Humans, Infrared Rays, Mice, Mice, Inbred C57BL, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Diabetes Mellitus, Experimental metabolism, Endothelium, Vascular metabolism, Endothelium-Dependent Relaxing Factors metabolism, Light
- Abstract
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm
2 for 5min with 10min dark period). NOS inhibition with N-Nitroarginine methyl ester (L-NAME) or the NO scavenger Carboxy-PTIO (c-PTIO) tested the specificity of NO production. 4,5-Diaminofluorescein diacetate (DAF-2) measured NO in human dermal microvascular endothelial cells (HMVEC-d). R/NIR significantly increased vasodilation in wild type and NOS inhibited groups, however R/NIR dilation was totally abolished with c-PTIO and blood vessel denudation. Interestingly, the bath solution from intact R/NIR stimulated vessels could dilate light naïve vessels in a NO dependent manner. Characterization of the bath identified a NO generating substance suggestive of S-nitrosothiols or non heme iron nitrosyl complexes. Consistent with the finding of an endothelial source of NO, intracellular NO increased with R/NIR in HMVEC-d treated with and without L-NAME (1mM), yet c-PTIO (100µm) reduced NO production. R/NIR significantly dilated db/db blood vessels. In conclusion, R/NIR stimulates vasodilation by release of NO bound substances from the endothelium. In a diabetes model of endothelial dysfunction, R/NIR restores vasodilation, which lends the potential for new treatments for diabetic vascular disease., (Published by Elsevier Inc.)- Published
- 2017
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192. Thiolate-based dinitrosyl iron complexes: Decomposition and detection and differentiation from S-nitrosothiols.
- Author
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Keszler A, Diers AR, Ding Z, and Hogg N
- Subjects
- Animals, Cysteine analogs & derivatives, Cysteine chemistry, Cysteine pharmacology, Ferrous Compounds chemistry, Ferrous Compounds metabolism, Glutathione analysis, Glutathione chemistry, Humans, Hydrogen-Ion Concentration, Lipopolysaccharides pharmacology, Luminescence, MCF-7 Cells, Mice, Nitric Oxide analysis, Nitric Oxide metabolism, Nitrites analysis, Nitrites chemical synthesis, RAW 264.7 Cells, S-Nitrosothiols chemistry, S-Nitrosothiols metabolism, S-Nitrosothiols pharmacology, Spermine analogs & derivatives, Spermine pharmacology, Ferrous Compounds analysis, S-Nitrosothiols analysis
- Abstract
Dinitrosyl iron complexes (DNIC) spontaneously form in aqueous solutions of Fe(II), nitric oxide (NO), and various anions. They exist as an equilibrium between diamagnetic, dimeric (bi-DNIC) and paramagnetic, monomeric (mono-DNIC) forms. Thiolate groups (e.g., on glutathione or protein cysteine residues) are the most biologically relevant anions to coordinate to Fe(II). Low molecular weight DNIC have previously been suggested to be important mediators of NO biology in cells, and emerging literature supports their role in the control of iron-dependent cellular processes. Recently, it was shown that DNIC may be one of the most abundant NO-derived products in cells and may serve as intermediates in the cellular formation of S-nitrosothiols. In this work, we examined the stability of low molecular weight DNIC and investigated issues with their detection in the presence of other NO-dependent metabolites such as S-nitrosothiols. By using spectrophotometric, Electron Paramagnetic Resonance, ozone-based chemiluminesence, and HPLC techniques we established that at neutral pH, bi-DNIC remain stable for hours, whereas excess thiol results in decomposition to form nitrite. NO was also detected during the decomposition, but no S-nitrosothiol formation was observed. Importantly, mercury chloride accelerated the degradation of DNIC; thus, the implications of this finding for the diagnostic use of mercury chloride in the detection of S-nitrosothiols were determined in simple and complex biological systems. We conclude S-nitrosothiol levels may have been substantially overestimated in all methods where mercury chloride has been used., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
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193. Antagonistic Effects of Endogenous Nitric Oxide in a Glioblastoma Photodynamic Therapy Model.
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Fahey JM, Emmer JV, Korytowski W, Hogg N, and Girotti AW
- Subjects
- Adjuvants, Pharmaceutic pharmacology, Aminolevulinic Acid pharmacology, Animals, Apoptosis drug effects, Apoptosis radiation effects, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, Humans, Adjuvants, Pharmaceutic therapeutic use, Aminolevulinic Acid therapeutic use, Glioblastoma therapy, Nitric Oxide antagonists & inhibitors, Nitric Oxide Synthase Type II antagonists & inhibitors, Photochemotherapy
- Abstract
Gliomas are aggressive brain tumors that are resistant to conventional chemotherapy and radiotherapy. Much of this resistance is attributed to endogenous nitric oxide (NO). Recent studies revealed that 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has advantages over conventional treatments for glioblastoma. In this study, we used an in vitro model to assess whether NO from glioblastoma cells can interfere with ALA-PDT. Human U87 and U251 cells expressed significant basal levels of neuronal NO synthase (nNOS) and its inducible counterpart (iNOS). After an ALA/light challenge, iNOS level increased three- to fourfold over 24 h, whereas nNOS remained unchanged. Elevated iNOS resulted in a large increase in intracellular NO. Extent of ALA/light-induced apoptosis increased substantially when an iNOS inhibitor or NO scavenger was present, implying that iNOS/NO was acting cytoprotectively. Moreover, cells surviving a photochallenge exhibited a striking increase in proliferation, migration and invasion rates, iNOS/NO again playing a dominant role. Also observed was a large iNOS/NO-dependent increase in matrix metalloproteinase-9 activity, decrease in tissue inhibitor of metalloproteinase-1 expression and increase in survivin and S100A4 expression, each effect being consistent with accelerated migration/invasion as a prelude to metastasis. Our findings suggest introduction of iNOS inhibitors as pharmacologic adjuvants for glioblastoma PDT., (© 2016 The American Society of Photobiology.)
- Published
- 2016
- Full Text
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194. The role of red blood cell S-nitrosation in nitrite bioactivation and its modulation by leucine and glucose.
- Author
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Wajih N, Liu X, Shetty P, Basu S, Wu H, Hogg N, Patel RP, Furdui CM, and Kim-Shapiro DB
- Subjects
- Glucose metabolism, Humans, Leucine metabolism, Nitrosation, Vasodilation, Erythrocytes metabolism, Nitric Oxide metabolism, Nitrites metabolism, Oxygen metabolism
- Abstract
Previous work has shown that red blood cells (RBCs) reduce nitrite to NO under conditions of low oxygen. Strong support for the ability of red blood cells to promote nitrite bioactivation comes from using platelet activation as a NO-sensitive process. Whereas addition of nitrite to platelet rich plasma in the absence of RBCs has no effect on inhibition of platelet activation, when RBCs are present platelet activation is inhibited by an NO-dependent mechanism that is potentiated under hypoxia. In this paper, we demonstrate that nitrite bioactivation by RBCs is blunted by physiologically-relevant concentrations of nutrients including glucose and the important signaling amino acid leucine. Our mechanistic investigations demonstrate that RBC mediated nitrite bioactivation is largely dependent on nitrosation of RBC surface proteins. These data suggest a new expanded paradigm where RBC mediated nitrite bioactivation not only directs blood flow to areas of low oxygen but also to areas of low nutrients. Our findings could have profound implications for normal physiology as well as pathophysiology in a variety of diseases including diabetes, sickle cell disease, and arteriosclerosis., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
195. Nitric Oxide Suppresses β-Cell Apoptosis by Inhibiting the DNA Damage Response.
- Author
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Oleson BJ, Broniowska KA, Naatz A, Hogg N, Tarakanova VL, and Corbett JA
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Cell Survival, DNA Damage drug effects, Hep G2 Cells, Humans, Insulin-Secreting Cells cytology, Male, Mice, Organ Specificity, Phosphorylation drug effects, RAW 264.7 Cells, Rats, Rats, Sprague-Dawley, Signal Transduction drug effects, Camptothecin pharmacology, DNA Repair drug effects, Hydrogen Peroxide pharmacology, Insulin-Secreting Cells drug effects, Nitric Oxide metabolism
- Abstract
Nitric oxide, produced in pancreatic β cells in response to proinflammatory cytokines, plays a dual role in the regulation of β-cell fate. While nitric oxide induces cellular damage and impairs β-cell function, it also promotes β-cell survival through activation of protective pathways that promote β-cell recovery. In this study, we identify a novel mechanism in which nitric oxide prevents β-cell apoptosis by attenuating the DNA damage response (DDR). Nitric oxide suppresses activation of the DDR (as measured by γH2AX formation and the phosphorylation of KAP1 and p53) in response to multiple genotoxic agents, including camptothecin, H2O2, and nitric oxide itself, despite the presence of DNA damage. While camptothecin and H2O2 both induce DDR activation, nitric oxide suppresses only camptothecin-induced apoptosis and not H2O2-induced necrosis. The ability of nitric oxide to suppress the DDR appears to be selective for pancreatic β cells, as nitric oxide fails to inhibit DDR signaling in macrophages, hepatocytes, and fibroblasts, three additional cell types examined. While originally described as the damaging agent responsible for cytokine-induced β-cell death, these studies identify a novel role for nitric oxide as a protective molecule that promotes β-cell survival by suppressing DDR signaling and attenuating DNA damage-induced apoptosis., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
- Full Text
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196. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.
- Author
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Simeoni I, Stephens JC, Hu F, Deevi SV, Megy K, Bariana TK, Lentaigne C, Schulman S, Sivapalaratnam S, Vries MJ, Westbury SK, Greene D, Papadia S, Alessi MC, Attwood AP, Ballmaier M, Baynam G, Bermejo E, Bertoli M, Bray PF, Bury L, Cattaneo M, Collins P, Daugherty LC, Favier R, French DL, Furie B, Gattens M, Germeshausen M, Ghevaert C, Goodeve AC, Guerrero JA, Hampshire DJ, Hart DP, Heemskerk JW, Henskens YM, Hill M, Hogg N, Jolley JD, Kahr WH, Kelly AM, Kerr R, Kostadima M, Kunishima S, Lambert MP, Liesner R, López JA, Mapeta RP, Mathias M, Millar CM, Nathwani A, Neerman-Arbez M, Nurden AT, Nurden P, Othman M, Peerlinck K, Perry DJ, Poudel P, Reitsma P, Rondina MT, Smethurst PA, Stevenson W, Szkotak A, Tuna S, van Geet C, Whitehorn D, Wilcox DA, Zhang B, Revel-Vilk S, Gresele P, Bellissimo DB, Penkett CJ, Laffan MA, Mumford AD, Rendon A, Gomez K, Freson K, Ouwehand WH, and Turro E
- Subjects
- Case-Control Studies, DNA Copy Number Variations, Female, Genetic Association Studies methods, Humans, Male, Mutation, Polymorphism, Single Nucleotide, Sequence Analysis, DNA methods, Blood Platelet Disorders genetics, Genetic Predisposition to Disease, Hemorrhage genetics, High-Throughput Nucleotide Sequencing methods, Thrombosis genetics
- Abstract
Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD., (© 2016 by The American Society of Hematology.)
- Published
- 2016
- Full Text
- View/download PDF
197. ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia.
- Author
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Woodfin A, Beyrau M, Voisin MB, Ma B, Whiteford JR, Hordijk PL, Hogg N, and Nourshargh S
- Subjects
- Animals, Disease Models, Animal, Endotoxemia genetics, Endotoxemia pathology, Intercellular Adhesion Molecule-1 genetics, Mice, Mice, Knockout, Neutrophils pathology, Phagocytosis drug effects, Phagocytosis genetics, Reactive Oxygen Species metabolism, Transendothelial and Transepithelial Migration drug effects, Transendothelial and Transepithelial Migration genetics, Endotoxemia chemically induced, Endotoxemia metabolism, Gene Expression Regulation drug effects, Intercellular Adhesion Molecule-1 biosynthesis, Lipopolysaccharides toxicity, Neutrophils metabolism
- Abstract
Intracellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on the cell surface of numerous cell types such as endothelial and epithelial cells, vascular smooth muscle cells, and certain leukocyte subsets. With respect to the latter, ICAM-1 has been detected on neutrophils in several clinical and experimental settings, but little is known about the regulation of expression or function of neutrophil ICAM-1. In this study, we report on the de novo induction of ICAM-1 on the cell surface of murine neutrophils by lipopolysaccharide (LPS), tumor necrosis factor, and zymosan particles in vitro. The induction of neutrophil ICAM-1 was associated with enhanced phagocytosis of zymosan particles and reactive oxygen species (ROS) generation. Conversely, neutrophils from ICAM-1-deficient mice were defective in these effector functions. Mechanistically, ICAM-1-mediated intracellular signaling appeared to support neutrophil ROS generation and phagocytosis. In vivo, LPS-induced inflammation in the mouse cremaster muscle and peritoneal cavity led to ICAM-1 expression on intravascular and locally transmigrated neutrophils. The use of chimeric mice deficient in ICAM-1 on myeloid cells demonstrated that neutrophil ICAM-1 was not required for local neutrophil transmigration, but supported optimal intravascular and extravascular phagocytosis of zymosan particles. Collectively, the present results shed light on regulation of expression and function of ICAM-1 on neutrophils and identify it as an additional regulator of neutrophil effector responses in host defense., (© 2016 by The American Society of Hematology.)
- Published
- 2016
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198. A pro-tumorigenic function of S100A8/A9 in carcinogen-induced hepatocellular carcinoma.
- Author
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De Ponti A, Wiechert L, Schneller D, Pusterla T, Longerich T, Hogg N, Vogel A, Schirmacher P, Hess J, and Angel P
- Subjects
- Animals, Carcinoma, Hepatocellular pathology, Disease Models, Animal, Humans, Liver Neoplasms pathology, Male, Mice, Calgranulin A genetics, Calgranulin B genetics, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics
- Abstract
Human hepatocellular carcinoma (HCC) is a heterogeneous disease, driven by different risk factors and presenting diverse clinicopathological features and outcomes. Epidemiological and experimental data indicate that the damage-associated molecular pattern molecules S100A8 and S100A9, forming a heterodimer called calprotectin, might be critically involved in HCC development. However, deletion of S100a9 in an inflammation- and cirrhosis-driven mouse model did not show any impairment in liver tumorigenesis, most likely due to functional compensation by other inflammatory cytokines. Here, we investigated the effect of calprotectin ablation in mice treated with diethylnitrosamine, a carcinogen-driven HCC model mimicking cancer development caused by acute liver damage in the absence of prominent chronic inflammation and tissue damage. We found that tumor cell proliferation was diminished in the absence of S100A8/A9, leading to significant reduction of tumor size. Our results demonstrate that calprotectin is required for the progression of non-inflammation driven liver tumor and might represent a therapeutic target for the treatment of HCC formed in non-cirrhotic liver., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
199. Maggots as a wound debridement agent for chronic venous leg ulcers under graduated compression bandages: A randomised controlled trial.
- Author
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Davies CE, Woolfrey G, Hogg N, Dyer J, Cooper A, Waldron J, Bulbulia R, Whyman MR, and Poskitt KR
- Subjects
- Animals, Humans, Treatment Failure, Wound Healing, Wound Infection prevention & control, Compression Bandages, Debridement methods, Diptera growth & development, Larva, Varicose Ulcer therapy
- Abstract
Objectives: Slough in chronic venous leg ulcers may be associated with delayed healing. The purpose of this study was to assess larval debridement in chronic venous leg ulcers and to assess subsequent effect on healing., Methods: All patients with chronic leg ulcers presenting to the leg ulcer service were evaluated for the study. Exclusion criteria were: ankle brachial pressure indices <0.85 or >1.25, no venous reflux on duplex and <20% of ulcer surface covered with slough. Participants were randomly allocated to either 4-layer compression bandaging alone or 4-layer compression bandaging + larvae. Surface areas of ulcer and slough were assessed on day 4; 4-layer compression bandaging was then continued and ulcer size was measured every 2 weeks for up to 12 weeks., Results: A total of 601 patients with chronic leg ulcers were screened between November 2008 and July 2012. Of these, 20 were randomised to 4-layer compression bandaging and 20 to 4-layer compression bandaging + larvae. Median (range) ulcer size was 10.8 (3-21.3) cm(2) and 8.1 (4.3-13.5) cm(2) in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Mann-Whitney U test, P = 0.184). On day 4, median reduction in slough area was 3.7 cm(2) in the 4-layer compression bandaging group (P < 0.05) and 4.2 cm(2) (P < 0.001) in the 4-layer compression bandaging + larvae group. Median percentage area reduction of slough was 50% in the 4-layer compression bandaging group and 84% in the 4-layer compression bandaging + larvae group (Mann-Whitney U test, P < 0.05). The 12-week healing rate was 73% and 68% in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Kaplan-Meier analysis, P = 0.664)., Conclusions: Larval debridement therapy improves wound debridement in chronic venous leg ulcers treated with multilayer compression bandages. However, no subsequent improvement in ulcer healing was demonstrated., (© The Author(s) 2014.)
- Published
- 2015
- Full Text
- View/download PDF
200. Novel whole blood assay for phenotyping platelet reactivity in mice identifies ICAM-1 as a mediator of platelet-monocyte interaction.
- Author
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Armstrong PC, Kirkby NS, Chan MV, Finsterbusch M, Hogg N, Nourshargh S, and Warner TD
- Subjects
- Animals, Flow Cytometry, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Confocal, Phenotype, Sensitivity and Specificity, Blood Platelets metabolism, Intercellular Adhesion Molecule-1 metabolism, Monocytes metabolism, Platelet Aggregation physiology, Platelet Function Tests methods
- Abstract
Testing of platelet function is central to the cardiovascular phenotyping of genetically modified mice. Traditional platelet function tests have been developed primarily for testing human samples and the volumes required make them highly unsuitable for the testing of mouse platelets. This limits research in this area. To address this problem, we have developed a miniaturized whole blood aggregometry assay, based on a readily accessible 96-well plate format coupled with quantification of single platelet depletion by flow cytometric analysis. Using this approach, we observed a concentration-dependent loss of single platelets in blood exposed to arachidonic acid, collagen, U46619 or protease activated receptor 4 activating peptide. This loss was sensitive to well-established antiplatelet agents and genetic manipulation of platelet activation pathways. Observations were more deeply analyzed by flow cytometric imaging, confocal imaging, and measurement of platelet releasates. Phenotypic analysis of the reactivity of platelets taken from mice lacking intercellular adhesion molecule (ICAM)-1 identified a marked decrease in fibrinogen-dependent platelet-monocyte interactions, especially under inflammatory conditions. Such findings exemplify the value of screening platelet phenotypes of genetically modified mice and shed further light upon the roles and interactions of platelets in inflammation., (© 2015 by The American Society of Hematology.)
- Published
- 2015
- Full Text
- View/download PDF
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