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  • Gene
  • To examine whether these MAP kinases were involved in mediating heme oxygenase-1 gene expression, we utilized constitutively activated and dominant negative components of the ERK, JNK, and p38 MAP kinase signaling pathways. (umassmed.edu)
  • kinases
  • In LMH cells, sodium arsenite, cadmium, and heat shock, but not heme, induced activity of the MAP kinases extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. (umassmed.edu)
  • Hmox1
  • We report that expression of HO-1 dictates the pathologic outcome of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Induction of EAE in Hmox1-/- C57BL/6 mice led to enhanced CNS demyelination, paralysis, and mortality, as compared with Hmox1+/+ mice. (jci.org)
  • CoPPIX protection was abrogated in Hmox1-/- C57BL/6 mice, indicating that CoPPIX acts via HO-1 to suppress EAE progression. (jci.org)
  • HMOX1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian children," PLoS Pathogens , vol. 8, no. 3, Article ID e1002579, 2012. (hindawi.com)
  • Male and female transgenic mice overexpressing human HO-1 driven by the GFAP promoter (GFAP.HMOX1) and wild-type controls received striatal injections of autologous blood (25 μL). (sigmaaldrich.com)
  • protein
  • Nath K A, Vercellotti G M, Grande J P, et al (2001) Heme protein-induced chronic renal inflammation: suppressive effect of induced heme oxygenase-1. (springer.com)
  • Heme oxygenase-1 modulates thrombomodulin and activated protein c levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice," Experimental Lung Research , vol. 38, no. 4, pp. 173-182, 2012. (hindawi.com)
  • Challenge of macrophages with purified heme provoked nuclear translocation of Nrf2, and Nrf2 small interfering RNA resulted in significant inhibition of the ability of heme to induce HO-1 protein. (ahajournals.org)
  • However, an inducible protein transactivator is also probably necessary, as heme-induced HO-1 mRNA expression was fully inhibited by the protein synthesis inhibitor cycloheximide. (ahajournals.org)
  • Treatment of monocytes with hemin substantially inhibited HIV replication, as evident by nearly undetectable viral RNA and cell-free HIV-1 p24 protein in a dose-dependent manner. (jimmunol.org)
  • In addition to an increase in HO-1 protein expression, pentaerythritol tetranitrate but not isosorbide-5 mononitrate normalized vascular reactive oxygen species formation and augmented aortic protein levels of the tetrahydrobiopterin-synthesizing enzymes GTP-cyclohydrolase I and dihydrofolate reductase in angiotensin II-treated rats, thereby preventing endothelial NO synthase uncoupling. (ahajournals.org)
  • These two gases are linked in that NO can up-regulate HO-1 expression leading to the formation of endogenous CO ( 10 ), and CO can bind to the heme group in the iNOS protein and influence the production of NO ( 11 , 12 ). (rupress.org)
  • In addition, we measured levels of HO-1 mRNA and protein in the renal cortex. (asnjournals.org)
  • Toward this end, intrarenal HO-1 induction in response to four different experimental AKI models, and potential corresponding increases in plasma and urinary HO-1 protein concentrations, was sought. (asnjournals.org)
  • These plasma HO-1 increases were paralleled by stepwise increases in the levels of renal cortical HO-1 protein and HO-1 mRNA. (asnjournals.org)
  • Stepwise increases in plasma HO-1 levels were observed which mirrored increases in renal cortical HO-1 protein and mRNA levels. (asnjournals.org)
  • Prolonged shunting was associated with a tendency to decreased pulmonary gene and protein expressions of HO-1, while pulmonary gene expressions of interleukin (IL)-33, IL-19, intercellular adhesion molecule (ICAM)-1 and -2 were increased. (plos.org)
  • Pulmonary vascular resistance (evaluated by pressure/flow plots) was inversely correlated to pulmonary HO-1 protein and IL-19 gene expressions, and correlated to pulmonary ICAM-1 gene expression. (plos.org)
  • overexpression
  • In animal models, induction of HO-1 (by heme administration or adenovirus-mediated transgene overexpression) impedes the development of atherosclerotic lesions, whereas inhibition of HO-1 (by zinc protoporphyrin IX [ZnPPIX]) stimulates atherogenesis. (ahajournals.org)
  • Astrocyte overexpression of heme oxygenase-1 improves outcome after intracerebral hemorrhage. (sigmaaldrich.com)
  • In previous studies, HO-1 overexpression protected astrocytes from heme-mediated injury in vitro. (sigmaaldrich.com)
  • In the present study, we tested the hypothesis that selective astrocyte overexpression of HO-1 improves outcome after intracerebral hemorrhage. (sigmaaldrich.com)
  • Selective HO-1 overexpression in astrocytes reduces mortality, blood-brain barrier disruption, perihematomal cell injury, and neurological deficits in an autologous blood injection intracerebral hemorrhage model. (sigmaaldrich.com)
  • 5 The crucial role of the NADPH oxidase as an important superoxide source was further substantiated by the demonstration that NADPH oxidase 1 overexpression in transgenic mice potentiates AT-II-induced hypertension, 6 whereas blood pressure responses to AT-II were reduced in NADPH oxidase 1-deficient mice. (ahajournals.org)
  • HO-1 overexpression has been demonstrated to be cytoprotective in multiple models including endotoxemia ( 3 ), shock ( 4 ), ischemia/reperfusion ( 5 , 6 ), and xenograft rejection ( 7 ). (rupress.org)
  • free heme
  • Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis. (rcsb.org)
  • A. Ferreira, J. Balla, V. Jeney, G. Balla, and M. P. Soares, "A central role for free heme in the pathogenesis of severe malaria: the missing link? (hindawi.com)
  • Induction
  • Ren H, Leib S L, Ferriero D M, et al (2007) Induction of haem oxygenase-1 causes cortical non-haem iron increase in experimental pneumococcal meningitis: evidence that concomitant ferritin up-regulation prevents iron-induced oxidative damage. (springer.com)
  • Induction of HO-1 by cobalt protoporphyrin IX (CoPPIX) administration after EAE onset reversed paralysis in C57BL/6 and SJL/J mice and disease relapse in SJL/J mice. (jci.org)
  • HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. (ahajournals.org)
  • Conclusions- Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response. (ahajournals.org)
  • The guanine-thymidine (GT) n repeats in the HO-1 promoter determine HO-1 induction level. (ersjournals.com)
  • 14 Moreover, in human airway smooth muscle, HO-1 induction reduced cellular ROS production, 15 indicating that HO-1 and/or its products may regulate ROS production. (ahajournals.org)
  • We, therefore, set out to test the hypothesis that NO may modulate intracellular ROS production by NADPH oxidase via induction of HO-1 in HMECs. (ahajournals.org)
  • This report describes a biological function of this molecule in inducing host defense against HIV-1 infection via heme oxygenase-1 (HO-1) induction. (jimmunol.org)
  • Suppression of HIV replication in hemin-activated cells correlated with the induction of HO-1 and was attenuated by tin protoporphyrin (SnPP) IX, an inhibitor of HO-1 activity, suggesting a pivotal role of this endogenous enzyme in the regulation of HIV infection. (jimmunol.org)
  • Although numerous previous and recently published reports have demonstrated multiple prominent actions of HO-1 induction in various anti-inflammatory processes, its role in the regulation of HIV-1 infection is not known. (jimmunol.org)
  • Haploinsufficiency of HO-1 completely abolished the beneficial effects of pentaerythritol tetranitrate in angiotensin II-treated mice, whereas HO-1 induction by hemin (25 mg/kg) mimicked the effect of pentaerythritol tetranitrate. (ahajournals.org)
  • Improvement of vascular function in this particular model of arterial hypertension by pentaerythritol tetranitrate largely depends on the induction of the antioxidant enzyme HO-1 and identifies pentaerythritol tetranitrate, in contrast to isosorbide-5 mononitrate, as an organic nitrate able to improve rather than to worsen endothelial function. (ahajournals.org)
  • We hypothesized that in some cases CO requires up-regulation of iNOS and production of NO in mediating protective effects and that subsequent NO generation requires HO-1 induction to mediate its therapeutic effects. (rupress.org)
  • We measured plasma and urinary levels of HO-1 by ELISA during the induction and/or maintenance phases of four mouse models of AKI: ischemia/reperfusion, glycerol-induced rhabdomyolysis, cisplatin nephrotoxicity, and bilateral ureteral obstruction. (asnjournals.org)
  • Moreover, after induction of experimental autoimmune encephalomyelitis, mice with myeloid-specific HO-1 deficiency developed a higher incidence and an exacerbated, nonremitting clinical disease correlating with persistent activation of antigen-presenting cells, enhanced infiltration of Th17 cells, and a nonregressing myelin-specific T cell reactivity. (rupress.org)
  • EPS did not promote the intracellular accumulation of free ferrous ion and reactive oxygen species, by increasing ferritin via Nrf2 during HO-1 induction. (go.jp)
  • Hmox
  • Both Hmox isoforms might be largely responsible for the recycling of iron by its liberation from heme and hemoproteins, although their contribution to total iron homeostasis has not been carefully examined. (pnas.org)
  • activation
  • Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1," International Immunopharmacology , vol. 20, no. 1, pp. 24-32, 2014. (hindawi.com)
  • Moreover, the heme oxygenase-1 end product bilirubin directly inhibited fully functional NADPH oxidase and seemed to interrupt the assembly and activation of the oxidase. (ahajournals.org)
  • In experimental inflammatory autoimmune disorders such as encephalomyelitis and colitis ( 7 , 8 ), protective functions of HO-1 have been shown to be associated with the activation of the immune system. (jimmunol.org)
  • In addition to conditions related to immune and inflammatory responses, the life cycle of HIV-1 is closely associated with the activation state of its host cells. (jimmunol.org)
  • We demonstrate that myeloid HO-1 is required for the activation of interferon (IFN) regulatory factor (IRF) 3 after Toll-like receptor 3 or 4 stimulation, or viral infection. (rupress.org)
  • We have reported that epalrestat (EPS), which is currently used for the treatment of diabetic neuropathy, increases HO-1 levels through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in bovine aortic endothelial cells. (go.jp)
  • In this study, we tested the hypothesis that EPS upregulates HO-1 via Nrf2 activation in the component cells of the nervous system, by using rat Schwann cells and human SH-SY5Y cells. (go.jp)
  • It also markedly increased HO-1 levels in SH-SY5Y cells through the activation of Nrf2. (go.jp)
  • protective
  • Exogenous CO mimicked these effects, suggesting that CO contributes to the protective action of HO-1. (jci.org)
  • HO-1 along with its reaction products bilirubin and CO are protective against ischemia-induced injury (myocardial infarction, ischemia-reperfusion (IR)-injury and post-infarct structural remodelling). (biomedsearch.com)
  • As opposed to these curative potentials, the long-believed protective effect of HO-1 in cardiac remodelling in response to pressure overload and type 2 diabetes mellitus (DM) has been questioned by recent work. (biomedsearch.com)
  • Heme oxygenase -1 (HO-1) play a protective antioxidant role in the lung. (ersjournals.com)
  • Aims To evaluate the correlation of HO-1 polymorphisms to functional and exposure parameters in DTs and the protective role of HO-1 on Be Oxide (BeO) exposed A549 epithelial cells apoptosis. (ersjournals.com)
  • Decrease apoptosis in BeO-exposed A549 epithelial cells by hemin may indicate a protective role of HO-1. (ersjournals.com)
  • Our results indicate that suppression of NADPH oxidase-dependent reactive oxygen species formation may represent a novel mechanism underlying the cardiovascular protective actions of heme oxygenase-1 and bilirubin. (ahajournals.org)
  • When protection from cell death is initiated by CO, NO production and HO-1 activity are each required for the protective effect showing for the first time an essential synergy between these two molecules in tandem providing potent cytoprotection. (rupress.org)
  • We and others have previously demonstrated that iNOS/NO is protective in models of fulminant hepatic failure ( 1 , 2 ). (rupress.org)
  • Additionally, the protective effects initiated by CO are ultimately mediated, in part, via up-regulation of HO-1. (rupress.org)
  • catabolism
  • The pathophysiological functions of HO-1 have been associated with its enzymatic activities in heme catabolism. (rupress.org)
  • physiological
  • We will first review the physiological role of HO-1 as determined by the analysis of HO-1-deficient individuals. (springer.com)
  • Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. (abcam.com)
  • therefore, heme oxygenase-1 monitoring may prove useful for the identification of physiological stress inducers. (clontech.com)
  • right ventricular
  • Pulmonary arterial hypertension (PAH) is a rare and fatal disease characterized by abnormal pulmonary vasoconstriction and pulmonary arteriolar remodeling both leading to a progressive increase in pulmonary vascular resistance (PVR) and eventual right ventricular (RV) failure [1] . (plos.org)
  • functional
  • For instance, dietary iron deficiency results in millions of cases of anemia yearly, while functional hypoferremia contributes to the anemia that is frequently observed in chronic inflammatory diseases ( 1 ). (pnas.org)
  • Over the past decades, investigations of the functional role of HO-1 activity have greatly enhanced our understanding of this enzyme as a cellular defense mechanism against stress-related and various other pathogenic conditions ( 2 , 3 , 4 , 5 ). (jimmunol.org)
  • cellular
  • From these facts, it is clear that dissociation of iron from heme moieties and subsequent cellular release constitute a major component of iron homeostasis. (pnas.org)
  • Autoimmunity
  • This will be followed by an examination of the effect of HO-1 within immunopathological contexts such as immune disorders (autoimmunity and allergy) or infections. (springer.com)
  • enzymes
  • Both HO-1 and iNOS are cytoprotective enzymes and when expressed produce therapeutic benefits in a number of conditions/diseases. (rupress.org)
  • mRNA
  • We identified heme oxygenase-1 (HO-1) mRNA as a novel target of miR-1207-5p by western blotting and Ago2 immunoprecipitation. (nih.gov)
  • In iron-challenged, cultured proximal tubule cells, we observed a positive correlation between HO-1 mRNA level and HO-1 release. (asnjournals.org)
  • A proximal tubule cell-specific correlation between intracellular HO-1 mRNA and HO-1 release was also assessed in a cell culture (HK-2)-based system. (asnjournals.org)
  • superoxide dismutase
  • We demonstrated for the first time that EPS upregulates HO-1, superoxide dismutase, and catalase by activating Nrf2. (go.jp)
  • Vitro
  • The findings from this study demonstrate that hemin-mediated augmentation of HO-1 activity substantially suppresses HIV replication both in vitro and in vivo with no apparent toxic effects. (jimmunol.org)
  • hemoglobin
  • We found that erythrocytes, hemoglobin, or purified heme similarly induced CD163 and suppressed HLA-DR and reactive oxygen species. (ahajournals.org)
  • renal
  • Given the important role of HO-1 in determining renal responses to injury, it would be highly desirable to have a biomarker of its intrarenal activity. (asnjournals.org)
  • immune
  • A growing body of evidence points toward the capacity of this molecule to inhibit immune reactions and the pivotal role of HO-1 in inflammatory diseases. (springer.com)
  • Finally, we will review the molecular basis of HO-1 actions on different immune cells. (springer.com)
  • Notably, these defects were rectified by exogenous administration of IFN-β, confirming that HO-1 functions directly upstream of this critical immune pathway. (rupress.org)
  • These results uncover a novel direct function for myeloid HO-1 in the regulation of IFN-β production, establishing HO-1 as a critical early mediator of the innate immune response. (rupress.org)
  • regulation
  • Nevertheless, the mechanisms and regulation of heme iron reutilization are poorly understood. (pnas.org)
  • 15 Taken together, these antiatherogenic properties of HO-1 suggest a prominent role for HO-1 in the genetic regulation in the development of atherosclerosis. (ahajournals.org)
  • These challenges, coupled with emerging regulatory mechanisms, motivate further in-depth studies to help understand untapped layers of HO-1 regulation and action. (biomedsearch.com)
  • neuroinflammation
  • In conclusion, HO-1 or exposure to its end product CO counters autoimmune neuroinflammation and thus might be used therapeutically to treat MS. (jci.org)
  • vascular
  • We hypothesized that altered HO-1 signalling could be involved in both pulmonary vascular and RV changes. (plos.org)