Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of the carbon monoxide (CO) producing enzymes haem oxygenase (HO) type 1 and 2 were studied in the feline lower oesophageal sphincter (LOS), as were HO activity and functional effects of CO. HO-2 immunoreactivity was observed in nerve cell bodies in the submucosal and myenteric plexus, nerve fibres, non-neuronal cells surrounding smooth muscle bundles, and in arterial endothelium, HO-1 immunoreactivity was confined to non-neuronal cells in the smooth muscle layer. CO production, indicating HO activity, was demonstrated in tissue homogenates. CO relaxed the LOS, and activated the cyclic GMP system. These results show that HO is present in the LOS, and suggest that CO can be generated by neuronal and non-neuronal structures and may have a role as a peripheral messenger.
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PMID:Carbon monoxide as a putative messenger molecule in the feline lower oesophageal sphincter of the cat. 748 31

Presently we have investigated the carbon monoxide generating capacity of the cardiovascular system under normal and stress conditions by examining the microsomal heme oxygenase system at the transcript, protein and activity levels; and have assessed response of heart nitric oxide (NO) synthase activity and cyclic GMP levels to stress. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2, catalyze the rate limiting step in the only known pathway in eukaryotes for the generation of the potential cellular message, carbon monoxide, and the antioxidant, bilirubin. We show expression of HO-1 and HO-2 at both the transcription and protein levels under normal conditions in the heart and descending aorta, and demonstrate the sensitivity of only the HO-1 isozyme to heat stress in these tissues. The ratio of the two HO-2 homologous transcripts (approximately 1.9 and 1.3 Kb) present in the atrium, ventricles and descending aorta and their levels were not altered by hyperthermia (42 degrees C, 20 min) when measured 1 or 6 hr after treatment. In contrast, hyperthermia caused a rapid, robust and coordinate increase of approximately 10- to 32-fold in the approximately 1.8-Kb HO-1 mRNA in these tissues when measured 1-hr post-treatment. Hyperthermia also caused a significant increase in both HO-1 protein and heme degradation capacity in the heart. Furthermore, the induction of HO-1 protein in the heart was accompanied by a significant elevation in tissue cyclic GMP level first detected 1-hr post-treatment and was sustained 6 hr after heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3':5'-guanosine monophosphate. 752 27

Two mechanisms contribute to cGMP formation by soluble guanylyl cyclase (i) NO production by NO synthase and (ii) CO production by heme oxygenase. We analyze here the contributions of these two pathways to IL1, TNF, lipopolysaccharide and hemin treated brain capillary endothelial cells. Cytokines and LPS induced cGMP formation in manners that were completely prevented by LY 83,583, methylene blue and by cyclosporin A. They were partially inhibited by inhibitor of NO synthase. Cyclosporin A acts by a posttranscriptional mechanism. Cells constitutively expressed mRNAs for heme oxygenase-1. Expression was enhanced by hemin but not by IL1 or lipopolysaccharide. Induction of heme oxygenase-1 and its inhibition by Sn protoporphyrin IX had no effect on cGMP levels.
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PMID:Contributions of NO synthase and heme oxygenase to cGMP formation by cytokine and hemin treated brain capillary endothelial cells. 754 88

Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 microM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cell which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.
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PMID:Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. 759 90

1. Carbon monoxide (CO), produced by haem oxygenase through degradation of haem, has been claimed to be a neuromessenger and a possible regulator of vascular tone. We examined whether the haem oxygenase inhibitor, zinc protoporphyrin-IX (ZnPP) and other porphyrins affect the relaxation evoked by various agents in the rat isolated aorta. 2. Pretreatment with ZnPP (0.1 mM) virtually abolished the relaxation evoked by vasoactive intestinal peptide (VIP) and atrial natriuretic peptide (ANP). ZnPP also evoked a rightward shift of the concentration-response curve for the relaxation induced by acetylcholine. 3. In contrast, ZnPP did not affect the relaxation evoked by forskolin and 3-morpholino-sydnonimine, agents which directly activate adenylate and guanylate cyclase, respectively. 4. Although, less effective than ZnPP, tin protoporphyrin-IX (SnPP; 0.1 mM) and protoporphyrin-IX (PP; 0.1 mM) also attenuated the VIP-evoked relaxation. 5. The elevation of cyclic AMP and cyclic GMP levels evoked by VIP and ANP, respectively, were abolished by pretreatment with ZnPP (0.1 mM). 6. ZnPP, SnPP and PP did not affect the contraction evoked by phenylephrine. 7. The results show that ZnPP inhibits relaxation induced by VIP, ANP and acetylcholine, probably by interfering with membrane receptor-coupled signal transduction pathways. This inhibition does not seem to be dependent upon inhibition of haem oxygenase. The lack of specificity of the haem oxygenase inhibiting metalloporphyrins makes them less suitable as pharmacological tools in the investigation of a messenger role for CO.
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PMID:Inhibition by zinc protoporphyrin-IX of receptor-mediated relaxation of the rat aorta in a manner distinct from inhibition of haem oxygenase. 764 74

Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.
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PMID:Carbon monoxide: a putative neural messenger. 809 63

We have investigated the role of carbon monoxide (CO) in lucigenin-dependent chemiluminescence of alveolar macrophages from rat lungs. CO (10 nM to 1 microM) decreased chemiluminescence of alveolar macrophages in a concentration-dependent fashion. At a concentration of 1 microM, CO significantly increased intracellular cyclic GMP levels from a control value of 175 +/- 25 fmol/2 x 10(6) cells to 431 +/- 49 fmol/2 x 10(6) cells. Pretreatment of alveolar macrophages with NG-monomethyl-L-arginine (100 microM) failed to inhibit CO (1 microM)-induced decreases in chemiluminescence of alveolar macrophages (3.7 +/- 0.7 cpm x 10(3) in the presence of NG-monomethyl-L-arginine and 3.4 +/- 0.6 cpm x 10(3) in the absence of NG-monomethyl-L-arginine) and CO (1 microM)-induced increases in intracellular cyclic GMP levels (452 +/- 65 fmol/2 x 10(6) cells in the presence of NG-monomethyl-L-arginine and 419 +/- 58 fmol/2 x 10(6) cells in the absence of NG-monomethyl-L-arginine). Decreases in chemiluminescence of alveolar macrophages induced by CO (1 microM) were concentration-dependently inhibited by methylene blue (from 0.1 microM to 10 microM). Dibutyryl cyclic GMP (db cyclic GMP) (1 mM) also reduced chemiluminescence of alveolar macrophages (1.5 +/- 0.3 cpm x 10(3) in the presence of db cyclic GMP and 3.6 +/- 0.6 cpm x 10(3) in the absence of db cyclic GMP). In contrast to CO and db cyclic GMP, zinc protoporphyrin-9 (10nM to microM), an inhibitor of heme oxygenase potentiated chemiluminescence of alveolar macrophages in a concentration-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of carbon monoxide in lucigenin-dependent chemiluminescence of rat alveolar macrophages. 778 3

Carbon monoxide (CO) generated by heme oxygenase has recently been considered a neural messenger in brain. This observation prompted us to investigate whether CO participates in vascular regulation in the liver, another organ with high levels of heme oxygenase activity. In isolated perfused rat liver, submicromolar levels of CO were detectable in the effluent and were able to be suppressed by the administration of Zn protoporphyrin IX (1 microM), a potent inhibitor of heme oxygenase. Furthermore, zinc protoporphyrin IX (1 microM) promoted an increase in the perfusion pressure under the constant flow conditions. These changes were reversed by adding CO (2 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. The present findings indicate that CO can function as an endogenous modulator of vascular perfusion in the liver.
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PMID:Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. 780 66

Carbon monoxide (CO) is a product of the enzyme heme oxygenase (HO; EC 1.14.99.3). In vascular smooth muscle cells, exogenously administered CO increases cyclic guanosine 3',5'-monophosphate (cGMP), which is an important regulator of vessel tone. We report here that smooth muscle cells produce CO via HO and that it regulates cGMP levels in these cells. Hypoxia, which has profound effects on vessel tone, significantly increased the transcriptional rate of the HO-1 gene resulting in corresponding increases of its mRNA and HO enzymatic activity. In addition, under the same conditions, rat aortic and pulmonary artery smooth muscle cells accumulated high levels of cGMP following a similar time course to that of HO-1 production. The increased accumulation of cGMP in smooth muscle cells required the enzymatic activity of HO, since it was abolished by a specific HO inhibitor, tin protoporphyrin. In contrast, N omega-nitro-L-arginine, a potent inhibitor of nitric oxide (NO) synthesis, had no effect on cGMP produced by smooth muscle cells, indicating that NO is not responsible for the activation of guanylyl cyclase in this setting. Furthermore, conditioned medium from hypoxic smooth muscle cells stimulated cGMP production in recipient cells and this stimulation was completely inhibited by tin protoporphyrin or hemoglobin, an inhibitor of CO production and a scavenger of CO, respectively. This report shows that HO-1 is expressed by vascular smooth muscle cells and that its product, CO, may regulate vascular tone under physiologic and pathophysiologic (such as hypoxic) conditions.
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PMID:Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. 787 3

Carbon monoxide is produced from a variety of sources in biological systems. Heme oxygenase and heme oxygenase-like activity is the predominant source in mammals, and may be equally important in plants and lower animals. The enzyme appears to be ubiquitous, highly conserved throughout phylogeny, and tightly regulated during development. This and other evidence suggests that heme oxygenase has an important physiological role, of which CO production may be a part. Other minor sources of CO include the oxidation of organic molecules. This includes the following: (1) auto-oxidation of phenols, flavenoids, and halomethanes; (2) photo-oxidation of organic compounds; and (3) lipid peroxidation of membrane lipids. No longer thought of as a waste product only, recent studies suggest that in the central nervous system cellular CO production can influence cGMP levels through effects on soluble guanylyl cyclase activity. Cellular CO production may also be linked to cell-cell interactions, and may be important in the cell's response to environmental changes. Whether CO will have a place similar to nitric oxide in cellular metabolism is still unclear, but it is apparent that these metabolic relationships will become increasingly complex. Cellular heme oxygenase activity results in the equimolar production of CO and bilirubin for each molecule of heme degraded. The CO thus formed diffuses into the blood, is carried via hemoglobin, and is excreted in the lungs. Therefore, CO production can be assessed clinically by measuring the rate of total body CO excretion, blood COHb levels, and end-tidal CO concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sources of carbon monoxide (CO) in biological systems and applications of CO detection technologies. 820 83


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