UMLS:C0031511 - FACTA Search

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Query: UMLS:C0031511 (pheochromocytoma)
14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phytobilin chromophores of phycobiliproteins and phytochromes are biosynthesized from heme in a pathway that begins with the opening of the tetrapyrrole macrocycle of protoheme to form biliverdin IX alpha, in a reaction catalyzed by heme oxygenase. A gene containing an open reading frame with a predicted polypeptide that has a sequence similar to that of a conserved region of animal microsomal heme oxygenases was identified in the published genomic sequence of Synechocystis sp. PCC 6803. This gene, named ho1, was cloned and expressed in Escherichia coli under the control of the lacZ promoter. Cells expressing the gene became green colored due to the accumulation of biliverdin IX alpha. The size of the expressed protein was equal to the predicted size of the Synechocystis gene product, named HO1. Heme oxygenase activity was assayed in incubations containing extract of transformed E. coli cells. Incubations containing extract of induced cells, but not those containing extract of uninduced cells, had ferredoxin-dependent heme oxygenase activity. With mesoheme as the substrate, the reaction product was identified as mesobiliverdin IX alpha by spectrophotometry and reverse-phase HPLC. Heme oxygenase activity was not sedimented by centrifugation at 100, 000 g. Expression of HO1 increased several-fold during incubation of the cells for 72 h in iron-deficient medium.
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PMID:Phytobilin biosynthesis: cloning and expression of a gene encoding soluble ferredoxin-dependent heme oxygenase from Synechocystis sp. PCC 6803. 974 99

The phytobilin chromophores of phycobiliproteins and phytochromes are biosynthesized from heme in a pathway that begins with the opening of the tetrapyrrole macrocycle of protoheme to form biliverdin IXalpha, in a reaction catalyzed by heme oxygenase. An Arabidopsis thaliana hy1 mutant was previously shown to be deficient in phytochrome responses, and these responses were regained when the plants were administered biliverdin IXalpha. A heme oxygenase-encoding gene, ho1, was recently cloned from the cyanobacterium Synechocystis sp. PCC 6803. When ho1 was expressed in Escherichia coli, the cells produced active ferredoxin-dependent soluble heme oxygenase. The open reading frame of ho1 was fused in frame with a chloroplast transit peptide-encoding sequence from the oli gene of Antirrhinum majus. This construct was placed in a binary plasmid vectorcontaining a kanamycin resistance marker and a cauliflower mosaic virus 35S promoter to control expression of the chimeric oli-ho1 gene and used to transform A. thaliana hy1 plants. Two independent transformed lines were obtained that had the phenotype of the parental Landsberg erecta line and expressed the chimeric gene, as indicated by detection of its mRNA by reverse transcriptase-polymerase chain reaction. The results indicate that Synechocystis sp. PCC 6803 heme oxygenase encoded by ho1 can substitute for the defective HY1 gene product and that the only required enzyme activity of the HY1 gene product is heme oxygenase.
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PMID:Phytobilin biosynthesis: the Synechocystis sp. PCC 6803 heme oxygenase-encoding ho1 gene complements a phytochrome-deficient Arabidopsis thalianna hy1 mutant. 1094 78

An efficient bacterial expression system of cyanobacterium Synechocystis sp. PCC 6803 heme oxygenase gene, ho-1, has been constructed, using a synthetic gene. A soluble protein was expressed at high levels and was highly purified, for the first time. The protein binds equimolar free hemin to catabolize the bound hemin to ferric-biliverdin IX alpha in the presence of oxygen and reducing equivalents, showing the heme oxygenase activity. During the reaction, verdoheme intermediate is formed with the evolution of carbon monoxide. Though both ascorbate and NADPH-cytochrome P450 reductase serve as an electron donor, the heme catabolism assisted by ascorbate is considerably slow and the reaction with NADPH-cytochrome P450 reductase is greatly retarded after the oxy-heme complex formation. The optical absorption spectra of the heme-enzyme complexes are similar to those of the known heme oxygenase complexes but have some distinct features, exhibiting the Soret band slightly blue-shifted and relatively strong CT bands of the high-spin component in the ferric form spectrum. The heme-enzyme complex shows the acid-base transition, where two alkaline species are generated. EPR of the nitrosyl heme complex has established the nitrogenous proximal ligand, presumably histidine 17 and the obtained EPR parameters are discriminated from those of the rat heme oxygenase-1 complex. The spectroscopic characters as well as the catabolic activities strongly suggest that, in spite of very high conservation of the primary structure, the heme pocket structure of Synechocystis heme oxygenase isoform-1 is different from that of rat heme oxygenase isoform-1, rather resembling that of bacterial heme oxygenase, H mu O.
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PMID:Expression and characterization of cyanobacterium heme oxygenase, a key enzyme in the phycobilin synthesis. Properties of the heme complex of recombinant active enzyme. 1258 Dec 8

Two isoforms of a heme oxygenase gene, ho1 and ho2, with 51% identity in amino acid sequence have been identified in the cyanobacterium Synechocystis sp. PCC 6803. Isoform-1, Syn HO-1, has been characterized, while isoform-2, Syn HO-2, has not. In this study, a full-length ho2 gene was cloned using synthetic DNA and Syn HO-2 was demonstrated to be highly expressed in Escherichia coli as a soluble, catalytically active protein. Like Syn HO-1, the purified Syn HO-2 bound hemin stoichiometrically to form a heme-enzyme complex and degraded heme to biliverdin IXalpha, CO and iron in the presence of reducing systems such as NADPH/ferredoxin reductase/ferredoxin and sodium ascorbate. The activity of Syn HO-2 was found to be comparable to that of Syn HO-1 by measuring the amount of bilirubin formed. In the reaction with hydrogen peroxide, Syn HO-2 converted heme to verdoheme. This shows that during the conversion of hemin to alpha-meso-hydroxyhemin, hydroperoxo species is the activated oxygen species as in other heme oxygenase reactions. The absorption spectrum of the hemin-Syn HO-2 complex at neutral pH showed a Soret band at 412 nm and two peaks at 540 nm and 575 nm, features observed in the hemin-Syn HO-1 complex at alkaline pH, suggesting that the major species of iron(III) heme iron at neutral pH is a hexa-coordinate low spin species. Electron paramagnetic resonance (EPR) revealed that the iron(III) complex was in dynamic equilibrium between low spin and high spin states, which might be caused by the hydrogen bonding interaction between the distal water ligand and distal helix components. These observations suggest that the structure of the heme pocket of the Syn HO-2 is different from that of Syn HO-1.
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PMID:Protein expressed by the ho2 gene of the cyanobacterium Synechocystis sp. PCC 6803 is a true heme oxygenase. Properties of the heme and enzyme complex. 1569 34

Bcl-X(L), a mitochondrial membrane protein, blocks apoptosis induced by a wide array of death signals. In spite of extensive research, the molecular milieu that characterizes the anti-apoptotic function of Bcl-X(L) is complex and not fully clarified. In the present work, we have investigated the role of Bcl-X(L) in protecting against oxidative death induced by H(2)O(2) in cultured rat pheochromocytoma (PC12) cells. PC12 cells exposed to H(2)O(2) underwent apoptotic cell death as determined by internucleosomal DNA fragmentation and an increased pro-apoptotic Bax to anti-apoptotic Bcl-X(L) ratio. Moreover, stable transfection with the bcl-X(L) gene rescued PC12 cells from apoptotic death caused by H(2)O(2). PC12 cells overexpressing bcl-X(L) exhibited relatively high constitutive transcriptional as well as DNA binding activities of NF-kappaB, compared with the vector-transfected control cells. Addition of NF-kappaB inhibitors, such as parthenolide and N-tosyl-L-phenylalanine chloromethyl ketone, to the media aggravated H(2)O(2)-induced oxidative cell death. PC12 cells transfected with bcl-X(L) exhibited higher levels of the heme oxygenase-1, which may confer these cells protection against oxidative stress. These results suggest that the redox-sensitive transcription factor NF-kappaB may play a role in bcl-X(L)-mediated protection against oxidative cell death.
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PMID:Possible role of NF-kappaB in Bcl-X(L) protection against hydrogen peroxide-induced PC12 cell death. 1572 Aug 30

Phycobiliproteins, light-harvesting proteins in cyanobacteria, red algae, and cryptophytes, contain phycobilin pigments. Phycobilins are synthesized from biliverdin, which is produced by the oxidative cleavage of the heme porphyrin ring catalyzed by heme oxygenase (HO). Two paralogs of ho (ho1 and ho2) have been identified in the genome of the cyanobacterium, Synechocystis sp. PCC 6803. The recombinant proteins of both paralogs (Syn HO-1 and Syn HO-2) possess in vitro heme degradation activity. We have determined the crystal structures of Syn HO-2 in complex with heme (heme-Syn HO-2) and its reduced and NO bound forms. The heme-Syn HO-2 crystal was a nonmerohedral twin, and detwinned diffraction data were used to refine the structure. Although heme-Syn HO-2 shares common folding with other HOs, the C-terminal segment is ordered and turns back to the heme-binding side. Gel-filtration chromatography analysis and molecular packing in the crystal indicate that heme-Syn HO-2 forms a homodimer, in which the C-terminal ordered segments interact with each other. Because Syn HO-2 is a monomer in the apo state, the dimeric interaction may aid in the selection of the reducing partner but likely does not interfere with heme binding. The heme iron is coordinated by a water molecule in the ferric form, but the distal water is absent in the ferrous form. In all of the Syn HO-2 structures, several water molecules form a hydrogen-bond network at the distal hemepocket, which is involved in HO activity. Upon NO binding, the side-chain conformation of Tyr 156 changes. Tyr 156 is located at the hydrophobic cluster, which interrupts the possible H(+) pathway from the molecular surface to the hemepocket. Thus, Tyr 156 may function as a H(+) shuttle by changing conformation.
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PMID:Crystal structure of dimeric heme oxygenase-2 from Synechocystis sp. PCC 6803 in complex with heme. 1576 54

Carbon monoxide (CO) is produced during the heme catabolism by heme oxygenase. In brain or blood vessels, CO functions as a neurotransmitter or an endothelial-derived relaxing factor. To verify whether crystallographically proposed CO-trapping sites of rat and cyanobacterial heme oxygenase-1 really work, heme catabolism by heme oxygenase-1 from rat and cyanobacterial Synechocystis sp. PCC 6803 has been scrutinized in the presence of 2-propanol. If 2-propanol occupies the trapping sites, formation of CO-bound verdoheme should be enhanced. Although effects of 2-propanol on the rat heme oxygenase-1 reaction were obscure, the reaction of cyanobacterial enzyme in the presence of NADPH/ferredoxin reductase/ferredoxin was apparently affected. Relative amount of CO-verdoheme versus CO-free verdoheme detected by optical absorption spectra increased as the equivalent of 2-propanol increased, thereby supporting indirectly that the hydrophobic cavity in cyanobacterial enzyme traps CO to reduce CO inhibition of verdoheme degradation.
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PMID:Evidence for the hydrophobic cavity of heme oxygenase-1 to be a CO-trapping site. 1612 69

The gene alr0617, from the cyanobacterium Anabaena sp. PCC7120, which is homologous to cpeS from Gloeobacter violaceus PCC 7421, Fremyella diplosiphon (Calothrix PCC7601), and Synechococcus sp. WH8102, and to cpcS from Synechococcus sp. PCC7002, was overexpressed in Escherichia coli. CpeS acts as a phycocyanobilin: Cys-beta84-phycobiliprotein lyase that can attach, in vitro and in vivo, phycocyanobilin (PCB) to cysteine-beta84 of the apo-beta-subunits of C-phycocyanin (CpcB) and phycoerythrocyanin (PecB). We found the following: (a) In vitro, CpeS attaches PCB to native CpcB and PecB, and to their C155I-mutants, but not to the C84S mutants. Under optimal conditions (150 mm NaCl and 500 mm potassium phosphate, 37 degrees C, and pH 7.5), no cofactors are required, and the lyase had a Km(PCB) = 2.7 and 2.3 microm, and a kcat = 1.7 x 10(-5) and 1.1 x 10(-5) s(-1) for PCB attachment to CpcB (C155I) and PecB (C155I), respectively; (b) Reconstitution products had absorption maxima at 619 and 602 nm and fluorescence emission maxima at 643 and 629 nm, respectively; and (c) PCB-CpcB(C155I) and PCB-PecB(C155I), with the same absorption and fluorescence maxima, were also biosynthesized heterologously in vivo, when cpeS was introduced into E. coli with cpcB(C155I) or pecB(C155I), respectively, together with genes ho1 (encoding heme oxygenase) and pcyA (encoding PCB:ferredoxin oxidoreductase), thereby further proving the lyase function of CpeS.
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PMID:Chromophore attachment to phycobiliprotein beta-subunits: phycocyanobilin:cysteine-beta84 phycobiliprotein lyase activity of CpeS-like protein from Anabaena Sp. PCC7120. 1645 71

A regulatory gene, designated pfsR (photosynthesis, Fe homeostasis and stress-response regulator), was discovered by a genetic screen in Synechocystis PCC 6803. Deletion of the gene from a high light-sensitive strain lacking four hli genes (4Xhli) restored viability to the parental strain under high light conditions. The quintuple mutant pfsR-/4Xhli retained photosystem-II and oxygen evolution capacity at levels similar to the wild-type levels under high light conditions. The transcripts of the two bfr genes (encoding bacterioferritin) were found to be constitutively up-regulated, whereas the transcripts of ho1 gene (encoding a heme oxygenase) were greatly down-regulated in high light upon deletion of pfsR. Under intermediate high intensity light, the pfsR deletion strains accumulated carotenoids and chlorophyll a to a significantly higher level than their corresponding parental strains. An exacerbated, transient increase in oxygen evolution during the early hours of high light acclimation and a somewhat increased steady-state level of photosystem-II-mediated oxygen evolution observed in the 4Xhli strain were brought back to the wild-type levels upon deletion of pfsR from the strain. The pfsR deletion mutants were found to be less sensitive to iron limitation under low light conditions and to suffer less lipid peroxidation following exposure to high light. Therefore, inactivation of PfsR resulted in tighter control of iron availability, which in turn reduced oxidative stress during photosynthesis in high light. These studies have revealed a critical role of PfsR in regulation of iron homeostasis and stress response.
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PMID:Suppression of the lethality of high light to a quadruple HLI mutant by the inactivation of the regulatory protein PfsR in Synechocystis PCC 6803. 1691 46

Activation of transcription factor NF-E2-related factor 2 (Nrf2) is a key initiation step in the cellular protection against a broad range of chemical oxidative stresses. To gain insights into dopaminergic cell responses to pesticides, the present study was conducted to examine the effects of deltamethrin (DM), a prototype of widely used pyrithroid pesticides, on the activation and expression of Nrf2 in PC12 rat adrenal pheochromocytoma cells as a dopaminergic cell model. We found, for the first time, that DM enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-regulated genes in these cells. In addition, DM exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes, such as heme oxygenase-l (HO-1) and gamma-glutamylcysteine synthetase catalytic heavy subunit (GCSh). Furthermore, when cells were pretreated with N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), DM-induced Nrf2 signaling was suppressed. These results indicate that ROS is the mediator of nuclear Nrf2 accumulation. Taken together, these data clearly show that DM increases Nrf2 expression and activity and that ROS is one of the mediators of this process.
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PMID:Transcription factor Nrf2 activation by deltamethrin in PC12 cells: Involvement of ROS. 1754 May 21

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