Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmodium yoelii nigeriensis infection in albino mice caused a significant increase in hepatic heme level, the increase being concomitant with a rise in parasitemia. This elevated heme was found to be associated with all the subcellular fractions except the cytosol, where its content remained unaltered. Activity of heme oxygenase, the key enzyme responsible for catabolism of heme, also increased progressively with rise in parasitemia. Treatment of normal mice with cobalt chloride [60 mg (kg body wt)-1; subcutaneously] brought about a 150% increase in the level of heme oxygenase; similar treatment of infected mice at low parasitemia could induce the enzyme activity while at high parasitemia the enzymic activity remained unaltered as compared to untreated infected mice. In spite of an increased level of heme oxygenase in the cobalt-treated mice, the level of heme did not show any noticeable change. Oral administration of chloroquine [64 mg (kg body wt)-1 x 4 days] brought about a 56% reduction in the level of heme oxygenase of normal animals but there was no change in infected animals when compared with the corresponding untreated infected mice. However, the amount of chloroquine present in livers of normal and infected animals was not significantly different.
Exp Mol Pathol 1991 Aug
PMID:Status of hepatic heme and heme oxygenase during Plasmodium yoelii nigeriensis infection in mice. 188 69

Biliverdin reductase is the dual nucleotide-dependent cytosolic enzyme that converts biliverdin to the bile pigment, bilirubin, and displays extensive microheterogeneity in rat organs. The enzyme is unique in having two pH optima. The present study reports on the tissue-dependent pattern of developmental expression of the reductase in rat liver and brain. When analyzed by Western immunoblotting, two closely migrating immunoreactive proteins were detected in the liver cytosol during the first 2-3 weeks after birth; the protein with greater mobility was not detected in the liver of adult aged animals (6 months old) and was present at low levels in rats during the first week of life. The faster migrating protein was not detected in the brain cytosol at any stage of development. Furthermore, in the brain the total amount of enzyme protein increased as the animal matured, whereas in the liver the enzyme protein level decreased with age. When the purified enzyme was analyzed, age-related changes in the variant composition of the enzyme in the liver were noted. Although in both adult and newborn animals (14 days old) the purified enzyme, when subjected to isoelectric focusing, separates into five net charge forms (pl 6.23, 5.91, 5.76, 5.61, and 5.48), the relative abundance of the variants notably differed in the two preparations. In addition, when the purified preparations were subjected to two-dimensional electrophoresis, although both purified preparations separate into three molecular weight forms (Mr 30,400, 30,700, and 31,400) one species (Mr 31,400, pl = 5.77), which was very prominently expressed in the newborn, was essentially absent in the adult. Biliverdin reductase activity of the liver cytosol with both NADPH (pH 8.7) and NADH (pH 6.7) exhibited developmental changes, with the activity increasing after birth, reaching a peak on day 14, and decreasing to low levels in the adult. The existence of a close correlation between development of biliverdin reductase activity in the brain and liver and that of heme oxygenase in these organs is noted. The suggestion is made that the reductase is not a passive component of the heme degradation pathway; rather, its activity could become limiting in the elimination of heme degradation products.
Mol Pharmacol 1990 Oct
PMID:Multiple forms of biliverdin reductase: age-related change in pattern of expression in rat liver and brain. 223 89

The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2-isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S-transferase Ya/Yc subunit, UDP-glucuronosyltransferase isoenzyme (UDPGTr-2), NADPH-cytochrome P450 oxidoreductase, and 5-aminolevulinate synthase. When rats were treated with hemin, together with inducing drug, there was a marked reduction in the induced levels of these mRNAs, with decreases in the range of 55-95%. Basal levels of these mRNAs in the noninduced rat liver were also lowered by hemin administration. Nuclear run-on transcriptional experiments showed that hemin administration substantially lowered both the basal and drug-induced transcriptional activities of the genes for cytochrome P450IIB1/IIB2 and 5-aminolevulinate synthase. In contrast, the mRNA for heme oxygenase was elevated by hemin treatment, whereas the mRNA levels of beta-actin, albumin, and ornithine transcarbamylase, used as controls, were not affected. Treatment of rats with clofibrate resulted in increased levels of mRNA for cytochrome IVA1 and, in addition, those for cytochromes P450IIB1 and P450IIB2. Hemin administration repressed the induction of mRNA levels for cytochromes P450IIB1 and IIB2 but not that for cytochrome P450 IVA1. Additionally, the induction of P450IAI by beta-naphthoflavone was not affected by hemin. The results suggest that heme may negatively control the induction of cytochromes P450IIB1 and IIB2 and other hepatic enzymes by phenobarbitone and phenobarbitone-like drugs and perhaps play a role in regulating drug metabolism. There is, however, no evidence at present as to whether heme has a direct role in such a mechanism or whether injected hemin promotes a secondary response.
Mol Pharmacol 1990 Oct
PMID:Hemin administration to rats reduces levels of hepatic mRNAs for phenobarbitone-inducible enzymes. 223 90

Treatment of cultured human skin fibroblasts with near-UV radiation, hydrogen peroxide, and sodium arsenite induces accumulation of heme oxygenase mRNA and protein. In this study, these treatments led to a dramatic increase in the rate of RNA transcription from the heme oxygenase gene but had no effect on mRNA stability. Transcriptional activation, therefore, appears to be the major mechanism of stimulation of expression of this gene by either oxidative stress or sulfydryl reagents.
Mol Cell Biol 1990 Sep
PMID:Oxidant stress leads to transcriptional activation of the human heme oxygenase gene in cultured skin fibroblasts. 238 32

The regulation of cardiac heme oxygenase and cytochrome P-450 mixed function oxidase was studied in the rabbit heart. Heme oxygenase activity is found in ventricular and atrial microsomal fractions. This activity is NADPH dependent, and is inhibited by tin and zinc protoporphyrin, but not by either SKF 525A or 7,8-benzoflavone. Immunologic studies of cardiac heme oxygenase demonstrate that antibodies prepared against human purified hepatic heme oxygenase recognize rabbit atrial heme oxygenase and inhibit the enzyme activity by 92%. In contrast, control immunoglobulin does not inhibit heme oxygenase activity. Further, the western blotting technique demonstrates that a similar band of protein with a molecular weight of 32,000 exists in cardiac microsomes and that no protein cross-reacts with purified hepatocyte heme oxygenase. Marked induction of atrial heme oxygenase is observed in microsomal fractions prepared from rabbits treated with cobalt chloride. Atrial microsomes possess 0.24 nmol of cytochrome P-450 as compared to 0.68 nmol/mg protein in microsomes from the liver. The levels of aryl hydrocarbon hydroxylase (AHH) activity, a cytochrome P-450-dependent enzyme, in ventricle and atrium are stimulated by a NADPH-generating system and are sensitive to 7,8-benzoflavone, and SKF 525A, known inhibitors of cytochrome P-450 mixed function oxidase. AHH activity in ventricular and atrial microsomes is 2-3% of that seen in liver microsomes whereas the P-450 content/mg protein is about 20% of that observed in the liver. AHH activity is mediated by a form of cytochrome P-450 that is inducible by 3-methylcholanthrene/beta-naphthoflavone. A possible new role of the heart cytochrome P-450 system in cardiac function is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Jan
PMID:Identification of heme oxygenase and cytochrome P-450 in the rabbit heart. 355 Jan 6

The sulfhydryl agent, cysteamine (CSH), promotes the accumulation of autofluorescent, peroxidase-positive cytoplasmic granules in cultured astroglia akin to those which naturally accumulate in astrocytes of the aging periventricular brain. Both in vitro and in situ, CSH rapidly induces various heat shock proteins (HSP) in astrocytes long before granulation occurs. In the present study, we determined that CSH treatment resulted in an increase in HSP 27, HSP 90 and heme oxygenase (HO-1) at both the protein and mRNA level. We also showed that C6 glioma cells, unlike primary astrocytes, constitutively express HSP 27, HSP 90 and HO-1 at low levels. Moreover, CSH is incapable of eliciting further HSP expression or inducing granulation in the glioma cells. Our results support the hypothesis that the biogenesis of redox-active astrocytic inclusions in CSH-treated glial cultures and in the aging periventricular brain is dependent on an antecedent cellular stress response.
Brain Res Mol Brain Res 1995 Jul
PMID:Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells. 747 27

Gram-negative sepsis is the most common cause of the adult respiratory distress syndrome (ARDS). Lipopolysaccharide (LPS) when administered in vivo produces pathophysiologic changes similar to those seen in ARDS. The pathogenesis of these changes is mediated in part by oxidative stress. We demonstrate that LPS induces high mRNA levels of the stress-inducible gene heme oxygenase-1 (HO-1) in the rat lung. Increased HO-1 mRNA levels correlate with increased HO-1 protein and enzyme activity. Immunohistochemical analyses of lung tissues from rats treated with LPS reveal abundant HO-1 expression in inflammatory and bronchoalveolar epithelial cells. We further examined the molecular regulation of HO-1 gene expression after exposure of RAW 264.7 macrophage cells to LPS in vitro. These cells respond to LPS with increased HO-1 mRNA expression and HO-1 gene transcription. Transcriptional activation of the mouse HO-1 gene by LPS is mediated by a 5' distal enhancer fragment located approximately 4 kbp upstream from the transcription site. Electrophoretic mobility shift assays show increased activator protein-1 (AP-1) binding activity in RAW 264.7 cells after LPS treatment. Mutation of the AP-1 binding site in this enhancer fragment completely abolishes HO-1 gene activation while mutation of CCAAT/enhancer-binding protein (C/EBP) binding site exerts negligible effect, suggesting that the AP-1 family of transcription factors plays a critical role in regulating HO-1 gene activation following LPS treatment. Furthermore, upstream phosphorylation events modulate this AP-1-dependent expression of the HO-1 gene after LPS treatment.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Induction of heme oxygenase-1 gene expression by lipopolysaccharide is mediated by AP-1 activation. 754 68

In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding protein (C/EBP)-beta, and C/EBP-delta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-beta, and C/EBP-delta mRNA expression was correlated with increased DNA binding activity of the transcription factor complexes activator protein 1 and C/EBP in tissue lysates. Because oxidative damage plays an important role in the aging process and little is known about the susceptibility of aged rats to hyperoxia, we also examined the relative tolerance of old rats to hyperoxia. Surprisingly, we observed that aged rats exhibit greater tolerance to hyperoxic stress than young rats. Old rats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided with decreased albumin levels in bronchoalveolar lavage and the delayed onset of activation of transcription factors and expression of oxidative stress-inducible genes in old rats. Transcription factor and stress-response gene activation may serve as useful molecular markers for oxidant lung injury.
Am J Respir Cell Mol Biol 1995 Jul
PMID:Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats. 759 40

Heme oxygenase exists as two isoenzymes designated heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). HO-2 is made constitutively in many cell types whereas HO-1 is a stress protein inducible by heat, heavy metals, ultraviolet irradiation, and oxidative stress. Recombinant rat HO-1 was expressed in bacteria and antiserum designated HO-1713 was raised against the purified protein. HO-1713 detected recombinant rat HO-1 and recombinant rat HO-2. In rat tissues it detected HO-1 and a second, unidentified band designated HO-L (heme oxygenase-like immunoreactivity) which was not HO-2. Cultured rat cortical neurons and forebrain astrocytes were exposed to hydrogen peroxide (0.14-0.7 micromolar for 30 or 60 min). Neurons which contained little detectable HO-1 and which were sensitive to hydrogen peroxide at the high end of the dose curve failed to induce HO-1 by Western blot analysis. In contrast, cultured rat forebrain astrocytes which contained HO-1 under normal culture conditions and which were resistant to injury by hydrogen peroxide, increased their content of immunoreactive HO-1 by 7-fold within 3 h after exposure. Our results support a protective role for HO-1 in oxidative injury and suggest that the relative inability of neurons to increase HO-1 after oxidative stress may contribute to their selective vulnerability vis-a-vis astrocytes. They also suggest that differential expression of heme oxygenase in studies utilizing CNS cultures may alter normal cell physiology and cell survival.
Brain Res Mol Brain Res 1995 May
PMID:Differential expression of heme oxygenase-1 in cultured cortical neurons and astrocytes determined by the aid of a new heme oxygenase antibody. Response to oxidative stress. 760 42

In 1991, we postulated that carbon monoxide, which is formed endogenously from heme catabolism catalyzed by heme oxygenase and shares some of the chemical and biological properties of nitric oxide, may play a role similar to that of nitric oxide as a widespread signal transduction mechanism for the regulation of cell function and communication. We review the experimental evidence that tests this postulate. Carbon monoxide appears to be involved in the neurophysiological phenomenon of long-term potentiation, which appears to play a key role in memory and learning. Zinc protoporphyrin, an inhibitor of heme oxygenase, prevents induction of long-term potentiation. Zinc protoporphyrin is an endogenous substance, the levels of which are increased in iron deficiency states and in lead poisoning, and by inhibiting heme oxygenase may modulate long-term potentiation and memory. It has been shown that, when cobalt protoporphyrin is injected into the medial nuclei of the rat hypothalamus, weight loss occurs. These nuclei contain heme oxygenase, and we postulate that weight loss is due to cobalt protoporphyrin induction of heme oxygenase and increased formation of carbon monoxide, which serves as a signal transduction mechanism in the medial hypothalamus to suppress appetite.
Cell Mol Biol (Noisy-le-grand) 1994 Nov
PMID:Heme oxygenase: the physiological role of one of its metabolites, carbon monoxide and interactions with zinc protoporphyrin, cobalt protoporphyrin and other metalloporphyrins. 784 53


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