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 level of mRNA encoding beta-globin was examined in dimethyl sulfoxide (DMSO)-sensitive (DS), and DMSO-resistant (DR) murine erythroleukemia (MEL) cells. DR cells lack erythroid-specific delta-aminolevulinate (ALA) synthase (AL-AS-E), and fail to undergo erythroid differentiation following treatment with DMSO. Treatment of cells with DMSO markedly increased ALAS-E mRNA in DS cells, while the same treatment downregulated the nonspecific ALA synthase (ALAS-N) mRNA levels in both DS and DR cells. The levels of beta-globin mRNA, heme content, and hemoglobin in DS cells increased, while those in DR cells decreased following treatment with DMSO. Treatment of DR cells with hemin caused an increase in beta-globin mRNA and hemoglobin, and partially restored the DMSO-mediated suppression of beta-globin mRNA and hemoglobin synthesis. DMSO treatment decreased heme oxygenase (HO) mRNA in hemin-treated DS cells, but not in hemin-treated DR cells. These findings indicate that heme is necessary for accumulation of the beta-globin transcript during erythroid differentiation, and that hemin-mediated HO induction becomes markedly downregulated in differentiated erythroid cells, presumably because less free heme is available for HO induction by a greater demand for the synthesis of hemoglobin.
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PMID:Regulation of beta-globin mRNA accumulation by heme in dimethyl sulfoxide (DMSO)-sensitive and DMSO-resistant murine erythroleukemia cells. 812 58

Cyanobacteria, red algae, and cryptophytes contain phycobiliproteins which function as photosynthetic light-harvesting pigments. The chromophores of phycobiliproteins are phycobilins, open-chain tetrapyrroles that are synthesized from protoheme. The first step of phycobilin formation is the conversion of protoheme to biliverdin IX alpha in a reaction that is catalyzed by heme oxygenase. In the unicellular red alga, Cyanidium caldarium, light is required for the accumulation of phycobiliproteins. It has been reported previously that the synthesis of the apoprotein components of allophycocyanin and phycocyanin is induced by light in C. caldarium, that the phycobilin precursors, delta-aminolevulinic acid (ALA), protoporphyrin IX, and protoheme can substitute for light, and that the regulation is exerted at the level of mRNA synthesis. We have determined that a key enzyme of phycobilin formation is induced by light in C. caldarium. Extractable heme oxygenase activity is low in dark-grown cells, and it increases approximately 6-fold during the first 24 h after the cells are illuminated. After 24 h, the activity decreases to a level approximately equal to the initial activity. Heme oxygenase is induced in unilluminated cells by administration of ALA. D-Glucose, which is known to inhibit phycocyanin accumulation in C. caldarium, inhibits the induction of heme oxygenase by light or ALA. Induction of heme oxygenase by light or ALA is blocked by cycloheximide, an inhibitor of cytoplasmic protein synthesis, but not by chloramphenicol, an inhibitor of chloroplast protein synthesis. Rifampicin, an inhibitor of algal chloroplast RNA synthesis, and gabaculine, a competitive inhibitor of ALA biosynthesis, block the induction of heme oxygenase by light but not by ALA. These results indicate that heme oxygenase in C. caldarium is induced by phycobilin precursors. The induction by light and the repression of the induction by D-glucose are probably indirect effects mediated by the effects of light and D-glucose on phycobilin precursor formation. The results also indicate that heme oxygenase is encoded by a nuclear gene and is synthesized on cytoplasmic ribosomes.
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PMID:Regulation of heme oxygenase activity in Cyanidium caldarium by light, glucose, and phycobilin precursors. 814 49

Two blue bile pigments were formed under anaerobic conditions from the tetrapyrrole precursor delta-aminolevulinate by cells and cell extracts of Clostridium tetanomorphum. These compounds were also formed by cell extracts from the octacarboxylic tetrapyrrole, uroporphyrin III. Bactobilin, the first bacterial bile pigment to be discovered, is related to uroporphyrin I. The present results hence increase the number of bile pigments related to bactobilin. Bactobilin and its isomers differ markedly from the eukaryotic bile pigments which are all related to the dicarboxylic compound, protoporphyrin IX. The enzyme participating in the formation of the bacterial bile pigments was obligatorily anaerobic, in decided contrast to the only other known bile pigment-forming enzyme, the eukaryotic oxygen-requiring heme oxygenase.
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PMID:Anaerobic breakdown of uroporphyrins I and III to bile pigments by extracts of Clostridium tetanomorphum. 831 98

Eisai hyperbilirubinuria rat (EHBR) is a mutant strain which is originated from Sprague Dawley rats. The activities of heme metabolizing enzymes in EHBR were compared with those of Sprague Dawley rats as the control. The activity of delta-aminolevulinic acid (delta-ALA) synthetase, the initial and rate-limiting enzyme in heme biosynthesis, was significantly higher in the liver of EHBR. However, no significant difference in the activity of heme oxygenase, the first and rate-limiting enzyme in heme degradation, was observed in EHBR as compared to control rats. DDC, a porphyrinogenic agent, caused marked and prolonged increase in the activity of delta-ALA synthetase in EHBR. However, the contents of microsomal total heme and cytochrome P-450 were significantly decreased in EHBR 24 hrs after DDC injection. The activity of heme oxygenase by CdCl2, a inducer of heme oxygenase, was considerably higher in EHBR than in control rats. These results indicate some specific hypersensitivity for heme metabolizing enzymes in EHBR.
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PMID:Nature of heme metabolizing enzymes in a mutant rat with hyperbilirubinuria. 835 13

The effects of three calcium antagonists, nifedipine (NF), verapamil (V) and diltiazem (DL), on rat liver monooxygenases were studied. The drugs were administered in oral doses of 50, 40 and 30 mg/kg daily for 3 weeks in male Wistar rats. NF and V shortened the hexobarbital (HB) sleeping time and increased benzphetamin-N-demethylase (BND), ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), ethoxycoumarine-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD) and NADPH-cytochrome c reductase activities and the content of cytochrome P-450 and microsomal heme, but did not change the content of cytochrome b5. The data suggest that these calcium antagonists exert an enzyme-inducing effect on the hepatic monooxygenases. DL significantly increased only the EROD and NADPH-cytochrome c reductase activities and shortened HB sleeping time to a lesser extent, suggesting a weaker enzyme-inducing effect as compared to NF and V. The three drugs increased the delta-aminolevulinic acid (ALA) synthetase activity and decreased heme oxygenase (HO) activity. The increased cytochrome P-450 content is probably due to the increased synthesis and the decreased breakdown of this hemoprotein.
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PMID:On the enzyme-inducing action of calcium antagonists. 851 87

There is currently renewed interest in the biological significance of heme proteins. The most common heme proteins include hemoglobin, myoglobin, cytochromes, and redox enzymes such as catalase and peroxidase. Setaria digitata is a cattle filarial parasite, which is devoid of typical cytochrome systems. However, studies showed activities of delta Aminolevulinate synthase (ALAS), delta Aminolevulinate dehydratase (ALAD), and heme oxygenase in appreciable amounts, suggesting the presence of necessary equipment for the biosynthesis of heme. This is further confirmed by the end product inhibition of ALAS by heme and the observation of the death of the parasite by succinyl acetone, an inhibitor of the biosynthesis of heme. Though typical cytochrome systems are absent, microsomal cytochrome P 450 and elevated levels of heme containing enzymes such as catalase and peroxidase are present in the parasite. A unique hemoglobin is also detected which shows a difference in biological functions from the host system and that of the much-studied nematode parasite Ascaris sum.
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PMID:Presence and formation of heme and occurrence of certain heme proteins in the filarial parasite Setaria digitata. 987 18

Regulation of delta-aminolevulinic acid (ALA) synthase and heme oxygenase was analyzed in primary rat hepatocytes and in two immortalized cell lines, CWSV16 and CWSV17 cells. ALA synthase was induced by 4,6-dioxohepatnoic acid (4,6-DHA), a specific inhibitor of ALA dehydratase, in all three systems; however, the induction in CWSV17 cells was greater than in either of the other two systems. Therefore, CWSV17 cells were used to explore the regulation of both enzymes by heme and 4,6-DHA. Data obtained from detailed concentration curves demonstrated that 4,6-DHA induced the activity of ALA synthase once ALA dehydratase activity became rate-limiting for heme biosynthesis. Heme induced heme oxygenase activity with increases occurring at concentrations of 10 microM or greater. Heme blocked the 4,6-DHA-dependent induction of ALA synthase with an EC50 of 1.25 microM. Heme-dependent decreases of ALA synthase mRNA levels occurred more quickly and at lower concentrations than heme-dependent increases of heme oxygenase mRNA levels. ALA synthase mRNA remained at reduced levels for extended periods of time, while the increases in heme oxygenase mRNA were much more transient. The drastic differences in concentrations and times at which heme-dependent effects were observed strongly suggest that two-different heme-dependent mechanisms control the ALA synthase and heme oxygenase mRNAs. In CWSV17 cells, heme decreased the stability of ALA synthase mRNA from 2.5 to 1.3 h, while 4,6-DHA increased the stability of the mRNA to 5.2 h. These studies demonstrate that regulation of ALA synthase mRNA levels by heme in a mammalian system is mediated by a change in ALA synthase mRNA stability. The results reported here demonstrate the function of the regulatory heme pool on both ALA synthase and heme oxygenase in a mammalian hepatocyte system.
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PMID:Regulation of heme metabolism in rat hepatocytes and hepatocyte cell lines: delta-aminolevulinic acid synthase and heme oxygenase are regulated by different heme-dependent mechanisms. 1136 15

In the present study, we investigated the contribution of methylsulfonyl metabolite derived from 1,2,4-trichlorobenzene (1,2,4-TCB) on the delta-aminolevulinic acid (ALA) synthetase induction by the parent compound in rats. The time courses of increasing of hepatic microsomal total cytochrome P450 content after a single i.p. administration of 1,2,4-TCB (1.36 mmol/kg), and 2,3,5- and 2,4,5-trichlorophenyl methyl sulfones (2,3,5- and 2,4,5-TCPSO2Mes) (50 micromol/kg each) were in parallel with those of increasing of the total heme content in liver microsomes. 1,2,4-TCB significantly increased the heme oxygenase activity, but 2,3,5- and 2,4,5-TCPSO2Mes did not. On the other hand, 1,2,4-TCB and 2,3,5-TCPSO2Me markedly enhanced the ALA synthetase activity. No change was observed in this enzyme activity after the administration of 2,4,5-TCPSO2Me. After the administration of 1,2,4-TCB to the rats treated with DL-buthionine-(S,R)-sulfoximine (BSO) and to the non-BSO-treated rats, the concentrations of both 2,3,5- and 2,4,5-TCPSO2Mes were significantly lower in liver of the BSO-treated rats than in liver of the non-BSO-treated rats. Additionally, the 1,2,4-TCB did not elevate the ALA synthetase activity in the BSO-treated rats. On the other hand, the administration of 2,3,5-TCPSO2Me to BSO-treated rats resulted in induction of ALA synthetase. The results strongly suggest that the methyl sulfone derived from 1,2,4-TCB, i.e., 2,3,5-TCPSO2Me, contributes highly to the induction of the ALA synthetase activity by the parent compound.
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PMID:The contribution of 2,3,5-trichlorophenyl methyl sulfone, a metabolite of 1,2,4-trichlorobenzene, to the delta-aminolevulinic acid synthetase induction by 1,2,4-trichlorobenzene in rat liver. 1199 31

Vascular tissues express heme oxygenase, which metabolizes heme to form carbon monoxide (CO). CO promotes relaxation of vascular smooth muscle but also inhibits nitric oxide (NO) formation. This study examines the hypothesis that CO promotes endothelium- and NO synthase-dependent vasoconstriction of isolated arterioles. Studies were conducted on pressurized first-order gracilis muscle arterioles isolated from anesthetized male Sprague-Dawley rats. Exogenous CO, as well as a heme precursor, delta-aminolevulinic acid (delta-ALA), constricted arterioles with intact endothelium pretreated with phenylephrine; these effects were abolished by removal of the endothelium. CO- and delta-ALA-induced vasoconstrictions were converted to dilations by pretreatment with an inhibitor of NO synthase, Nomega-nitro-l-arginine methyl ester, or with Nomega-nitro-l-arginine methyl ester and an NO donor, sodium nitroprusside. Furthermore, CO-induced vasoconstriction was prevented by pretreatment with the NO synthase substrate l-arginine. This study shows that exogenous, as well as endogenously formed, CO can promote endothelium-dependent vasoconstriction in isolated gracilis muscle arterioles. Because CO-induced vasoconstriction is abolished by NO synthase blockade and by l-arginine, CO most likely promotes endothelium-dependent vasoconstriction by inhibiting endothelial NO formation.
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PMID:Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles. 1290 79

Hepatoerythropoietic porphyria (HEP) is the homozygous form of Porphyria Cutanea Tarda (PCT), characterized by an accumulation of porphyrins due to uroporphyrinogen decarboxylase deficiency. Fluorinated volatile anaesthetics are often used to produce general anaesthesia. Anaesthesia has certainly been implicated in the triggering of acute porphyria crisis. The effects of volatile anaesthetics in a B-lymphocyte cell line established from HEP patients (LBHEP) on heme metabolism have been investigated.LBHEP cells were exposed to sodium phosphate buffer containing dissolved Enflurane, Isoflurane or Sevoflurane (10mM) during 20min. Aminolevulinate synthase (ALA-S) activity, the regulatory enzyme of heme synthesis, was 300% induced by the anaesthetics. A 25-30% diminution of porphobilinogenase (PBG-ase) activity was found when Isoflurane or Sevoflurane were added to the cells, while no significant changes were detected after Enflurane treatment. Although some oxidative stress has been induced by the anaesthetics, reflected by the 35% diminution of glutathione (GSH), no alteration in heme oxygenase (HO) activity, the enzyme involved in heme breakdown and frequently induced as a response to stress stimuli, was observed. Studies using animals inoculated with LBHEP cells were also performed. Findings here described mimic biochemical alterations in the heme pathway, which are characteristic of another hepatic porphyria, similar to those previously reported when these anaesthetics were administered to animals, and they also advertise about the possible unsafe use of these drugs in the case of hepatic non-acute porphyrias.
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PMID:Volatile anaesthetics induce biochemical alterations in the heme pathway in a B-lymphocyte cell line established from hepatoerythropoietic porphyria patients (LBHEP) and in mice inoculated with LBHEP cells. 1464 87


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