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Haem Oxygenase (haem + oxygenase)
Selected AbstractsHaem oxygenase in enteric nervous system of human stomach and jejunum and co-localization with nitric oxide synthaseNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2001S. M. Miller Recent evidence suggests that carbon monoxide (CO) may be a neurotransmitter, similar to nitric oxide (NO) in the enteric nervous system. The distribution of haem oxygenase (HO), the biosynthetic enzyme for CO, has been determined in the enteric nervous system of animals, but little is known about the distribution of HO in human gastrointestinal tract. The present study investigated the expression of HO and its colocalization with NO synthase (NOS), the biosynthetic enzyme for NO, in human antrum and jejunum. HO isoforms were identified using immunohistochemistry and NOS was identified by immunohistochemistry or NADPH-d histochemistry. HO-2 immunoreactive (IR) cell bodies in enteric ganglia and nerve fibres in longitudinal and circular muscle were found in both antrum and jejunum. Co-localization of HO-2 and NOS was about 40% in HO-2 containing cell bodies of myenteric ganglia and only 10% or less in cell bodies of submucous ganglia. HO-1 immunoreactivity was not detected in antrum or jejunum. The results suggest that CO is produced in human enteric ganglion neurones and indicate a possible role of CO as a neurotransmitter and possible interaction between HO and NOS pathways in inhibitory neurotransmission in the human gastrointestinal tract. [source] Role of haem oxygenase-1 in microbial host defenceCELLULAR MICROBIOLOGY, Issue 2 2009Su Wol Chung Summary Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections. [source] Selectivity of imidazole,dioxolane compounds for in vitro inhibition of microsomal haem oxygenase isoformsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2006Robert T Kinobe Haem oxygenases (HO) are involved in the catalytic breakdown of haem to generate carbon monoxide (CO), iron and biliverdin. It is widely accepted that products of haem catabolism are involved in biological signaling in many physiological processes. Conclusions to most studies in this field have gained support from the judicious use of synthetic metalloporphyrins such as chromium mesoporphyrin (CrMP) to selectively inhibit HO. However, metalloporphyrins have also been found to inhibit other haem-dependent enzymes, such as nitric oxide synthase (NOS), cytochromes P-450 (CYPs) and soluble guanylyl cyclase (sGC), induce the expression of HO-1 or exhibit varied toxic effects. To obviate some of these problems, we have been examining non-porphyrin HO inhibitors and the present study describes imidazole,dioxolane compounds with high selectivity for inhibition of HO-1 (rat spleen microsomes) compared to HO-2 (rat brain microsomes) in vitro. (2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H -imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane hydrochloride) was identified as the most selective inhibitor with a concentration of 0.6 ,M inhibiting HO-1(inducible) by 50% compared with 394 ,M for HO-2 (constitutive). These compounds were found to have no effects on the catalytic activities of rat brain NOS and lung sGC, but were potent inhibitors of microsomal CYP2E1 and CYP3A1/3A2 activities. In conclusion, we have identified imidazole,dioxolanes that are able to inhibit microsomal HO in vitro with high selectivity for HO-1 compared to HO-2, and little or no effect on the activities of neuronal NOS and sGC. These molecules could be used to facilitate studies on the elucidation of physiological roles of HO/CO in biological systems. British Journal of Pharmacology (2006) 147, 307,315. doi:10.1038/sj.bjp.0706555 [source] Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorptionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2004G. O. Latunde-Dada Abstract Background, Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of ,-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. Design, We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. Results, While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 µmoles kg,1 body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. Conclusions, The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important. [source] Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healingJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 7 2008Kirill I. Shingel Abstract The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as ,solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds. Copyright © 2008 John Wiley & Sons, Ltd. [source] Haem oxygenase in enteric nervous system of human stomach and jejunum and co-localization with nitric oxide synthaseNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2001S. M. Miller Recent evidence suggests that carbon monoxide (CO) may be a neurotransmitter, similar to nitric oxide (NO) in the enteric nervous system. The distribution of haem oxygenase (HO), the biosynthetic enzyme for CO, has been determined in the enteric nervous system of animals, but little is known about the distribution of HO in human gastrointestinal tract. The present study investigated the expression of HO and its colocalization with NO synthase (NOS), the biosynthetic enzyme for NO, in human antrum and jejunum. HO isoforms were identified using immunohistochemistry and NOS was identified by immunohistochemistry or NADPH-d histochemistry. HO-2 immunoreactive (IR) cell bodies in enteric ganglia and nerve fibres in longitudinal and circular muscle were found in both antrum and jejunum. Co-localization of HO-2 and NOS was about 40% in HO-2 containing cell bodies of myenteric ganglia and only 10% or less in cell bodies of submucous ganglia. HO-1 immunoreactivity was not detected in antrum or jejunum. The results suggest that CO is produced in human enteric ganglion neurones and indicate a possible role of CO as a neurotransmitter and possible interaction between HO and NOS pathways in inhibitory neurotransmission in the human gastrointestinal tract. [source] Crystallization and preliminary crystallographic studies of Helicobacter pylori HugZ, a novel haem oxygenaseACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2009Fan Jiang The haem oxygenase HugZ is part of the iron-acquisition mechanism that is essential for the adaptive colonization of Helicobacter pylori, a major pathogen of gastroenteric diseases. The HugZ,haemin complex has been purified and crystallized and diffraction data sets have been collected to 1.8,Å resolution. The HugZ,haemin complex crystals belonged to space group P212121, with unit-cell parameters a = 88.40, b = 139.37, c = 152.97,Å. [source] Selective expansion of CD16highCCR2, subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammationCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005K. Mizuno Summary Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16highCCR2, subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-,, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16highCCR2, monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16lowCCR2+ subpopulation produced little. These results were contrary to the generally accepted notion that the CD16highCCR2, monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16highCCR2, subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16highCCR2, subpopulations are of a distinct lineage from CD16lowCCR2+ monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo. [source] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibodyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004Y. TAKEDA SUMMARY There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 µmol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21,24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon- , level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies. [source] Effect of N -acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic ratsCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 2 2009Gina Y Tsai MD Abstract Purpose:, The aim of this study is to investigate markers of inflammation and oxidative stress in an early model of diabetic retinopathy, correlate retinal and plasma results and evaluate the influence of treatment by N -acetylcysteine (NAC), a free radical scavenger. Methods:, Four groups were studied: control (C), streptozotocin (STZ)-induced diabetic rats (D), STZ rats following 8 weeks of NAC (DT), and control rats following 8 weeks of NAC (CT). Plasma levels of free 15-F2t-isoprostane (15-F-2t-IsoP), superoxide dismutase (SOD) and tumour necrosis factor-alpha (TNF-,) were obtained. Primary antibodies against macrophages (ED-1), microglia (Ox-42), pericytes (NG-2), endothelial and perivascular cells (IB-4), haem oxygenase 1 (HO-1) and vascular endothelial growth factor (VEGF) were used. Results:, Expression of NG-2 was robust in C, CT, DT, and mild in D. The intensity of IB-4 was higher in D and DT compared with the C and CT. Ox-42 and ED-1 expression was higher in the D than in the DT, C or CT. Expression of VEGF and HO-1 was non-specific across the four groups. Plasma levels of 15-F-2t-IsoP and TNF-, were higher in the D as compared with the C, CT and DT. SOD levels were lower in the D when compared with the C, CT and D. Conclusions:, Macrophage/microglia activation, pericyte loss and endothelial/perivascular cell changes occur early in the pathogenesis of DR. These changes are associated with an increase in plasma markers of oxidative stress and inflammation and are minimized by treatment with NAC. The results suggest that therapies that reduce free radicals will help minimize the early events in diabetic retinopathy in the STZ model. [source] Staphylococcus aureus haem oxygenases are differentially regulated by iron and haemMOLECULAR MICROBIOLOGY, Issue 5 2008Michelle L. Reniere Summary Iron acquisition is a vital process for most pathogenic bacteria, as iron is a limiting nutrient during infection. Staphylococcus aureus, an increasingly important pathogen, acquires iron from host haem via elaboration of the iron-regulated surface determinant system (Isd). IsdG and IsdI are haem oxygenases that have been proposed to degrade exogenous haem in the bacterial cytoplasm as a mechanism to liberate free iron for use as a nutrient source. Herein, we report that IsdG and IsdI are both important for S. aureus growth on haemin as a sole iron source and are necessary for full S. aureus pathogenesis. Investigations into the regulation of these enzymes revealed that IsdG and IsdI are differentially regulated by iron and haem through both transcriptional and post-transcriptional mechanisms. Additionally, IsdI was found to be expressed in infected tissues at the sites of abscess formation, suggesting that abscesses are iron-starved microenvironments inside the host. These findings suggest that S. aureus differentially regulates IsdG and IsdI in response to alterations in iron and haem availability during infection. [source] The role of carbon monoxide in the gastrointestinal tractTHE JOURNAL OF PHYSIOLOGY, Issue 2 2004Simon J. Gibbons Carbon monoxide (CO) is a biologically active product of haem metabolism that contributes to the normal physiology of the gastrointestinal tract. In this article, we review recent data showing that CO is an integral regulator of gastrointestinal motility and an important factor in the response to gastrointestinal injury. CO is generated by haem oxygenase-2 (HO-2), which is constitutively expressed in many inhibitory neurones of the vertebrate enteric nervous system. The membrane potential gradients along and across the muscle layers of the gastrointestinal tract require the generation of CO by haem oxygenase-2. The presence of CO is also necessary for normal inhibitory neurotransmission in circular smooth muscle and appears to permit nitric oxide-mediated inhibitory neurotransmission. Genetic deletion of the haem oxygenase-2 gene in mice slows gut transit. The other major CO synthetic enzyme, haem oxygenase-1 (HO-1) is induced under conditions of stress or injury. Recent studies have demonstrated that up-regulation of haem oxygenase-1 protects the gut from several types of gastrointestinal injury, suggesting that CO or induction of HO-1 may find therapeutic use in gastrointestinal diseases and injuries. Furthermore, it is anticipated that the understanding of CO-mediated signalling in the gastrointestinal tract will inform studies in other tissues that express haem oxygenases. [source] | |||||||||||||