Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “OXYGENASES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed1990

Heme oxygenase-2 mRNA: developmental expression in the rat liver and response to cobalt chloride.

We have previously identified two isozymes of heme oxygenase, HO-1 and HO-2, in the rat liver exhibiting vastly different molecular biochemical properties, including their responses to various chemical inducers. In the present study of the livers of fetal and newborn rats (-1 day to 21 days) we observed marked differences in the developmental pattern of expression of the transcripts for the two forms of heme oxygenase. In addition, the transcripts for HO-1 and HO-2 vary in their number and response to treatment with cobalt chloride. Specifically, using a full length cDNA probe for HO-2, we observed the 1.3-kb mRNA previously shown to encode HO-2 in the testis, as well as a second less abundant transcript of 1.9 kb. An HO-1 cDNA probe detected only the anticipated single transcript of 1.8 kb. The abundance of each HO-2 homologous transcript was unaffected by cobalt chloride treatment (4 or 24 h) in newborn (7 days old) and adult rats. The 1.8-kb HO-1 mRNA, however, was markedly increased in abundance in both age groups by this treatment. The 1.3-kb HO-2 mRNA level nearly doubled after parturition, but remained essentially unchanged during the first 2 weeks of life, and only modestly increased by age 21 days. At all stages of development, the relative abundance of the 1.3- and 1.9-kb transcripts remained unchanged. In the case of 1.8-kb HO-1 mRNA, the level of mRNA was relatively constant during the first week of life, but was substantially reduced by age 14 days, and was further decreased by age 21 days and in the adult animals. In adult rats, the abundance of the 1.3-kb HO-2 mRNA did not markedly increase over that detected in the course of the early postparturition developmental period. The data suggest that the abundance of the two HO-2 homologous transcripts is not readily subject to regulation by chemicals at any stage of development. The expression of HO-1, on the other hand, is subject to such regulation throughout life, and its high transcript abundance in newborn rats may well reflect availability of an endogenous inducer.

Animals↗
PubMed1977

A comparative study on the influence of cysteamine and metyrapone on mixed-function oxygenase activities in variously pretreated liver microsomes from rats and mice.

It has been found that metyrapone can inhibit both type I and type II mixed-function oxygenase reactions, while cysteamine inhibits only type I activity in this mammalian system. Following pretreatment with phenobarbital and 3-methylcholanthrene the half-maximal inhibiting concentrations for the O-demethylation of paranitranisol are increased for cysteamine and decreased for metyrapone. Both cysteamine and metyrapone give type II binding spectra with oxidized cytochrome P-450. The negative and positive peaks are at 393 and 426 nm respectively for metyrapone, and 410 and 434 nm for cysteamine. Cysteamine showed no binding comparable to that of metyrapone for reduced cytochrome P-450. Metyrapone showed little or no inhibition of the NADH cytochrome-c reductase (EC 1.6.1.1) or NADPH (EC 1.6.2.3) cytochrome-c reductase while cysteamine had a more or less strong inhibiting effect depending on the pretreatment of animals. Neither the binding to P-450 heme nor the inhibition of NADH and NADPH cytochrome-c reductase correlates well with cysteamine inhibition of total activity. It is therefore suggested that cysteamine reacts with an intermediate electron carrier of non-heme iron or glycoprotein character thus inhibiting mixed-function oxygenase activity.

Acetanilides↗
PubMed1977

Conformational changes associated with the reversible cold inactivation of ribulose-1,5-bisphosphate carboxylase-oxygenase.

Crystalline ribulose-1,5-bisphosphate carboxylase-oxygenase (3-phospho-D-glycerate carboxy-lyase (dimerising), EC 4.1.1.39) isolated from tobacco (Nicotiana tabacum L.) leaf homogenates is partially inactivated by cold treatment and fully reactivated by simple heating in the absence of sulfhydryl reagents and effectors. Since the reversible cold inactivation of this bifunctional enzyme does not involve a gross change in the association state of subunits, a subtle conformational change induced by low temperatures was implicated (Chollet, R. and Anderson, L.L. (1976) Arch. Biochem. Biophys. 176, 344-351). Chemical modification of the cold-inactivated and heat-reactivated enzymes by 5,5'-dithiobis-(2-nitrobenzoate) and p-mercuribenzoate at 25 degrees C revealed no difference in the number of free -SH groups per mol protein. However, the reactivity of the sulfhydryl residues on the inactivated protein was considerably greater than that of the reactivated enzyme. Pretreatment of the two proteins with sodium dodecyl sulfate completely abolished the difference in -SH reactivity, indicating its dependence on protein conformation. Both the cold-inactivated and heat-reactivated enzymes enhanced the fluorescence intensity of 8-anilino-1-naphthalenesulfonate (ANS) and caused a blue shift of the emission maximum from 510 to 472 nm. When the inactivated enzyme was reactivated by heating, the increase in catalytic activity was closely paralleled by a concomitant decrease in the fluorescence intensity of the ANS - protein complex at 25 degrees C. Fluorescence titration experiments revealed that the decrease in fluorescence intensity accompanying heat reactivation of the inactivated enzyme was due to a reduction in the number of hydrophobic sites available for ANS binding rather than to a change in the dissociation constant of the ANS - protein complex. These results indicate that the reversible cold inactivation of ribulose-1,5-bisphosphate carboxylase-oxygenase is associated with a reversible change in the conformation of the protein. This cold-induced conformational change resluts in a greater exposure of sulfhydryl groups and hydrophobic regions to the external environment and is closely paralleled by changes in the catalytic activity of the protein. By analogy to other oligomeric enzymes also subject to reversible cold inactivation, perhaps low temperatures induce a partial dissociation of the octameric structure of the hydrophobic catalytic subunits, but complete dissociation is arrested in some unknown manner by the small hydrophilic subunits.

Anilino Naphthalenesulfonates↗
PubMed1992

Importance of histidine residue 25 of rat heme oxygenase for its catalytic activity.

A truncated, soluble, and enzymatically active rat heme oxygenase lacking its membrane-associative, C-terminal segment was expressed in E. coli strain JM109. The roles of its four histidine residues were examined by determining the enzymatic activities of mutant enzymes in which each of these residues in turn was replaced by alanine. Mutation of histidine residue 25 to alanine resulted in marked decrease in activity for heme breakdown, indicating that this histidine residue has an important role in the heme oxygenase reaction.

Alanine↗
PubMed1994

Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia.

Heme oxygenase is a rate-limiting enzyme in heme catabolism, the end of which include iron, carbon monoxide and bilirubin. Expression of the inducible form of heme oxygenase (HO-1) was investigated in rat brain following 20 min of forebrain ischemia by Northern blot and in situ hybridization analyses. The level of HO-1 mRNA was undetectable in the cerebral cortex of sham control, but increased following ischemic insult, reached the maximum after 12 h of reperfusion, and then decreased. In sham control brain, HO-1 mRNA was detectable only in the scattered neuron-like cells within the dentate gyrus hilus. At 12 h of reperfusion, the remarkable increase in HO-1 mRNA levels was observed in both neuronal and glia-like cells distributed in the neocortex, hippocampus and thalamus.

Animals↗
PubMed1995

Cloning and expression in Escherichia coli of the gene encoding beta-C-4-oxygenase, that converts beta-carotene to the ketocarotenoid canthaxanthin in Haematococcus pluvialis.

In the green alga Haematococcus pluvialis the ketocarotenoid astaxanthin accumulates under stress conditions. Astaxanthin is a red carotenoid pigment which possess antioxidative activity. We have cloned the gene for beta-C-4 oxygenase (beta-carotene ketolase) from the green algae H. pluvialis. The cloning method took advantage of a strain of E. coli which was genetically engineered to produce beta-carotene. An expression cDNA library of H. pluvialis was transfected to cells of this strain and visually screened for brown-red pigmented colonies. One colony out of 100,000 transformants showed color change due to accumulation of canthaxanthin. The cDNA clone in this transformant colony encodes the enzyme beta-C-4 oxygenase that catalyzes the conversion of beta carotene to canthaxanthin via echinenone. This enzyme does not convert zeaxanthin to astaxanthin. It is concluded that in H. pluvialis astaxanthin is synthesized via canthaxanthin and therefore an additional enzyme is predicted, which converts canthaxanthin to astaxanthin.

Bacterial Proteins↗
PubMed1996

Reduced cytochrome P450 and increased heme oxygenase in liver during rabbit aflatoxicosis.

The administration of aflatoxin B1 (AFB1) in New Zealand rabbit for 5 days at a daily oral dose of 0.05 or 0.1 mg/kg decreased microsomal hepatic cytochrome P450 whereas a dose-dependent increase in the reduced microsomal 420 nm absorption occurred. The nature of such an absorption was then investigated. Either in vitro incubation of control microsomal proteins with AFB1 up to 800 microM and NADPH, or primary rabbit hepatocyte cultures exposure to AFB1 up to 30 microM for 24 to 72 h, failed to produce any 420 nm absorbing species, suggesting that the 420 nm absorption observed in vivo was due to an hemoprotein increase. Chemical reductions of microsomal proteins from AFB1-treated rabbits confirmed this hypothesis. Enzyme activity determinations revealed an increase in both microsomal heme oxygenase and NADPH-cytochrome c reductase activities in AFB1 treated rabbits, suggesting that the 420 nm absorption observed in vivo was related to a particular increase in heme oxygenase.

Animals↗
PubMedDate not supplied

Immunohistochemical detection of human placental cytochrome P-450-associated mono-oxygenase system inducible by maternal cigarette smoking.

Several xenobiotic-metabolizing mono-oxygenase activities, in conjunction with the immunohistochemical localization of the respective cytochrome P-450 forms, were investigated in placentae from smoking and non-smoking women. The antibodies used in the immunohistochemical analyses were monoclonal antibodies (MAbs) 1-7-1 and 2-66-3, prepared against the 3-methylcholanthrene-induced and phenobarbital-induced rat liver P-450, respectively. The mono-oxygenase activities were higher in placental microsomes from smokers, although no difference was observed in microsomal P-450 content. A distinct positive staining with MAb 1-7-1 was detectable in the trophoblastic layer of all placentae from smokers. In placentae from non-smokers, minimal cytoplasmic staining was observed in large villi in a few trophoblastic cells. The staining reaction was negative when MAb 2-66-3 or non-specific antibody were used. These results demonstrate that maternal cigarette smoking induces in the trophoblastic layer of the placenta a cytochrome P-450 form which is detectable immunohistochemically with the monoclonal antibody to 3-methylcholanthrene-inducible P-450 in rat liver.

Antibodies, Monoclonal↗
PubMed1996

Ligation of the iron in the heme-heme oxygenase complex: X-ray absorption, electronic absorption and magnetic circular dichroism studies.

Heme oxygenase (HO) catalyzes the first steps in the breakdown of heme to biliverdin and carbon monoxide. It is a membrane-bound protein that has been shown to exist in two isoforms, HO-1 and HO-2. Recently, a soluble, truncated form of rat HO-1 (rHO) lacking the 23 amino-acid membrane anchor has been expressed in E. coli. Extended X-ray absorption fine structure (EXAFS) data on ferric rHO and its fluoride derivative support assignment of the axial iron ligands as oxygen and/or nitrogen donors having distances similar to ferric myoglobin. The electronic absorption and magnetic circular dichroism (MCD) spectra of the ferric and ferrous protoheme complexes of rHO as well as various ligand adducts are very similar to the corresponding spectra of myoglobin. The present study is the first investigation of the heme-heme oxygenase complex with EXAFS and MCD spectroscopy and establishes that the proximal ligand to the heme in rHO is histidine. Furthermore, the close similarity between the electronic absorption and MCD spectra of ferric rHO and myoglobin over the pH range 6 to 10 is consistent with distal heme ligation of ferric rHO as a water molecule or hydroxide ion, depending on pH. Taken together and in conjunction with the results of earlier studies, EXAFS, electronic absorption, and MCD spectroscopy solidly establish that the ligands to the heme in rHO are identical to those in myoglobin, namely, histidine/H2O at low pH and histidine/OH at high pH.

Animals↗
PubMed1996

Immunocytochemical localization of heme oxygenase-2 in the rat cerebellum.

Carbon monoxide (CO) is a gas that can permeate biological membranes and it has been suggested that the gas plays a signaling role in the brain by activating soluble guanylyl cyclase (sGC). CO is generated by heme oxygenase during the conversion of heme to biliverdin. In this study, we raised an antiserum against the chemically synthesized amino-terminal fragment of heme oxygenase-2 (HO-2) and studied the distribution of this enzyme in the rat cerebellum by an immunocytochemical method. Immunoreactivity specific for HO-2 was observed only in neurons. In the Purkinje cells and the basket cells of the cerebellum, immunoreactivity was detected in the dendrites and the somata but not in the axon terminals, suggesting that CO might be liberated primarily from the dendrites and somata rather than from the axons in this region of the rat brain.

Amino Acid Sequence↗
PubMedDate not supplied

Ribulose 1,5-bisphosphate carboxylase-oxygenase. I. Structural, immunochemical and catalytic properties.

Some structural, immunochemical and catalytic properties are examined for ribulose 1,5-bisphosphate carboxylase-oxygenase from various cellular organisms including bacteria, cyanobacteria, algae and higher plants. The native enzyme molecular masses and the subunit polypeptide compositions vary according to enzyme sources. The molecular masses of the large and small subunits from different cellular organisms, on the other hand, show a relatively high homology due to their well-conserved primary amino acid sequence, especially that of the large subunit. In higher plants, the native enzyme and the large subunit are recognized by the antibodies raised against either the native or large subunit, whereas the small subunit apparently cross-reacts only with the antibodies directed against itself. A wide diversity exists, however, in the serological response of the native enzyme and its subunits with antibodies directed against the native enzyme or its subunits from different cellular organisms. According to numerous kinetic studies, the carboxylase and oxygenase reactions of the enzyme with ribulose 1,5-bisphosphate and carbon dioxide or oxygen require activation by carbon dioxide and magnesium prior to catalysis with ribulose 1,5-bisphosphate and carbon dioxide or oxygen. The activation and catalysis are also under the regulation of other metal ions and a number of chloroplastic metabolites. Recent double-labeling experiments using radioactive ribulose 1,5-bisphosphate and 14CO2 have elucidated the carboxylase/oxygenase ratios of the enzymes from different organisms. Another approach, i.e., genetic experiments, has also been used to examine the modification of the carboxylase/oxygenase ratio.

Catalysis↗
PubMed1996

Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia.

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxygenase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO-2. HO-1 protein was remarkably induced in brain following ischemia, while the level of HO-2 protein was not noticeably affected. The level of HO-1 protein expression was maximal at 12 h, which is in good agreement with the time course of the HO-1 mRNA induction. In the cortical mantle, most of the cells expressing increased HO-1 protein were identified as pyramidal neurons and astrocytes by their shapes and locations. In hippocampal CA-2 and CA-3 subfields, prominent induction was observed in astrocytes rather than in neuronal cells. By contrast, the HO-1 protein was not detected in the CA1 subfield following the insult, although the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes within the CA1 subfield, there may be an impairment of protein metabolism, preceding the delayed CA1 pyramidal cell losses.

Animals↗
PubMed1980

Induction of tryptophan oxygenase and tyrosine aminotransferase by metabolites of hydrocortisone.

Metabolites of hydrocortisone were isolated from rat liver on a preparative scale, fractionated by column chromatography on Sephadex Lh-20 and silica gel and tested for biological activity. Apart from the well known neutral metabolites, steroid glucuronides and sulfates, we obtained metabolite fractions containing non-conjugated steroidal carboxy acids and acid metabolites of unknown structure. One of these fractions induced tyrosine aminotransferase (EC 2.6.1.5) in adrenalectomized female rats but not tryptophan oxygenase (EC 1.13.11.11), whereas another one mainly increased activity of tryptophan oxygenase. The doses necessary to significantly induce both enzymes were much lower in case of these metabolites than in the case of hydrocortisone itself. The active fractions eluting from silica gel column were analyzed by thin-layer chromatography in two different solvent systems. Absence of hydrocortisone in these fractions could be clearly demonstrated. Furthermore, the active fractions eluting from the silica gel column were characterized by treatment with an extract from Helix pomatia and/or diazomethane and subsequent analysis by thin-layer chromatography. We conclude, considering the biological activity of some synthesized derivatives of hydrocortisone, that the biologically active components are acid metabolites of hydrocortisone which are not identical to any of the known metabolites.

Adrenal Glands↗
PubMed1992

Dark induction of haem oxygenase messenger RNA by haematoporphyrin derivative and zinc phthalocyanine; agents for photodynamic therapy.

Haematoporphyrin derivative is one of the main drugs currently used in clinical trials involving photodynamic therapy of cancer, and zinc phthalocyanine is being considered as one of several possible alternatives. We show that incubation of cultured human fibroblasts populations with either of the two drugs will lead to a sharp increase in the accumulation of the messenger RNA corresponding to haem oxygenase. Only cells incubated with haematoporphyrin derivative show additional enhancement of expression of this specific gene on exposure to red light. Since haem oxygenase induction appears to be a specific stress response that may be involved in cellular defence, such observations should be confirmed under conditions which would allow the clinical implications to be fully evaluated.

Cell Line↗
PubMed2005

Heme oxygenase and heme degradation.

The microsomal heme oxygenase system consists of heme oxygenase (HO) and NADPH-cytochrome P450 reductase, and plays a key role in the physiological catabolism of heme which yields biliverdin, carbon monoxide, and iron as the final products. Heme degradation proceeds essentially as a series of autocatalytic oxidation reactions involving heme bound to HO. Large amounts of HO proteins from human and rat can now be prepared in truncated soluble form, and the crystal structures of some HO proteins have been determined. These advances have greatly facilitated the understanding of the mechanisms of individual steps of the HO reaction. HO can be induced in animals by the administration of heme or several other substances; the induction is shown to involve Bach1, a translational repressor. The induced HO is assumed to have cytoprotective effects. An uninducible HO isozyme, HO-2, has been identified, so the authentic HO is now called HO-1. HOs are also widely distributed in invertebrates, higher plants, algae, and bacteria, and function in various ways according to the needs of individual species.

Animals↗
PubMed2005

Thirty years of microbial P450 monooxygenase research: peroxo-heme intermediates--the central bus station in heme oxygenase catalysis.

Oxygen has always been recognized as an essential element of many life forms, initially through its role as a terminal electron acceptor for the energy-generating pathways of oxidative phosphorylation. In 1955, Hayaishi et al. [Mechanism of the pyrocatechase reaction, J. Am. Chem. Soc. 77 (1955) 5450-5451] presented the most important discovery that changed this simplistic view of how Nature uses atmospheric dioxygen. His discovery, the naming and mechanistic understanding of the first "oxygenase" enzyme, has provided a wonderful opportunity and scientific impetus for four decades of researchers. This volume provides an opportunity to recognize the breakthroughs of the "Hayaishi School." Notable have been the prolific contributions of Professor Ishimura et al. [Oxygen and life. Oxygenases, Oxidases and Lipid Mediators, International Congress Series, Elsevier, Amsterdam, 2002], a first-generation Hayaishi product, to characterization of the cytochrome P450 monooxygenases.

Bacterial Proteins↗
PubMed2005

A kinetic study of the mechanism of conversion of alpha-hydroxyheme to verdoheme while bound to heme oxygenase.

O2-dependent reactions of the ferric and ferrous forms of alpha-hydroxyheme complexed with water-soluble rat heme oxygenase-1 were examined by rapid-scan stopped-flow measurements. Ferric alpha-hydroxyheme reacted with O2 to form ferric verdoheme with an O2-dependent rate constant of 4x10(5) M(-1) s(-1) at pH 7.4 and 9.0. A decrease of the rate constant to 2.8x10(5) M(-1) s(-1) at pH 6.5 indicates that the reaction proceeds by direct attack of O2 on the pi-neutral radical form of alpha-hydroxyheme, which is generated by deprotonation of the alpha-hydroxy group. The reaction of ferrous alpha-hydroxyheme with O2 yielded ferrous verdoheme in a biphasic fashion involving a new intermediate having absorption maxima at 415 and 815 nm. The rate constants for this two-step reaction were 68 and 145 s(-1). These results show that conversion of alpha-hydroxyheme to verdoheme is much faster than the reduction of coordinated iron (<1 s(-1)) under physiological conditions [Y. Liu, P.R. Ortiz de Montellano, Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1, J. Biol. Chem. 275 (2000) 5297-5307], suggesting that, in vivo, the conversion of ferric alpha-hydroxyheme to ferric verdoheme precedes the reduction of ferric alpha-hydroxyheme.

Animals↗
PubMed2005

Expanding the alkane oxygenase toolbox: new enzymes and applications.

As highly reduced hydrocarbons are abundant in the environment, enzymes that catalyze the terminal or subterminal oxygenation of alkanes are relatively easy to find. A number of these enzymes have been biochemically characterized in detail, because the potential of alkane hydroxylases to catalyze high added-value reactions is widely recognized. Nevertheless, the industrial application of these enzymes is restricted owing to the complex biochemistry, challenging process requirements, and the limited number of cloned and expressed enzymes. Rational and evolutionary engineering approaches have started to yield more robust and versatile enzyme systems, broadening the alkane oxygenase portfolio. In addition, metagenomic approaches provide access to many novel alkane oxygenase sequences.

Alkanes↗