Nitric-oxide Dioxygenase Function of Human Cytoglobin with Cellular Reductants and in Rat Hepatocytes

Gardner, Anne M.; Cook, Matthew R.; Gardner, Paul R.

doi:10.1074/jbc.m110.132340

Cited by 88 publications

(141 citation statements)

References 65 publications

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“…The high degree of co-expression with HO-1 is notable as HO-1 is an oxidative stress-inducible protein and enzymatic degradation of heme leads to the production of iron, biliverdin (an antioxidant) and CO (34). Cygb may therefore either be a heme substrate for HO-1 or alternatively, Cygb may, in these HO-1-expressing neurons, regulate the level of the gas-neurontransmitter CO produced by HO-1 in a similar way to that proposed for NO (18,19,21).…”

Section: Discussionmentioning

confidence: 99%

“…The Cygb expression patterns in the mouse brain were recently determined to be identical in the rat and human brain, demonstrating that the rodent brain can be used as a translational model for studying Cygb in humans, at least at the anatomical level (12,13). The function of Cygb remains largely unknown, but several studies have linked Cygb to reactive oxygen/nitrogen species (RNS) nitric oxide (NO) scavenging (14)(15)(16)(17)(18)(19)(20). Furthermore, Cygb overexpression protects against ischemic cell death in vivo (21), although not when expressed at endogenous levels (22).…”

Section: Introductionmentioning

confidence: 99%

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Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

2014

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Abstract. Cytoglobin (Cygb), a novel oxygen-binding protein, is expressed in the majority of tissues and has been proposed to function in nitric oxide (NO) metabolism in the vasculature and to have cytoprotective properties. However, the overall functions of Cygb remain elusive. Cygb is also expressed in a subpopulation of brain neurons. Recently, it has been shown that stress upregulates Cygb expression in the brain and the majority of neuronal nitric oxide synthase (nNOS)-positive neurons, an enzyme that produces NO, co-express Cygb. However, there are more neurons expressing Cygb than nNOS, thus a large number of Cygb neurons remain uncharacterized by the neurochemical content. The aim of the present study was to provide an additional and more detailed neurochemical phenotype of Cygb-expressing neurons in the rat hippocampus. The rat hippocampus was chosen due to the abundance of Cygb, as well as this limbic structure being an important target in a number of neurodegenerative diseases. Using triple immunohistochemistry, it was demonstrated that nearly all the parvalbumin-and heme oxygenase 1-positive neurons co-express Cygb and to a large extent, these neuron populations are distinct from the population of Cygb neurons co-expressing nNOS. Furthermore, it was shown that the majority of neurons expressing somastostatin and vasoactive intestinal peptide also co-express Cygb and nNOS. Detailed information regarding the neurochemical phenotype of Cygb neurons in the hippocampus can be a valuable tool in determining the function of Cygb in the brain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

2014

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“…Human HbA was from John Olson (Department of Biochemistry and Cell Biology, Rice University, Houston, TX). Recombinant rat cyt b 5 , mouse Ngb, Ec MnSOD, Ec flavoHb, Ca flavoHb, Sc flavoHb, and Re flavoHb were prepared as described (27,28). Sodium (bi)sulfite, pH 7.2, stock 1.0 M solutions were prepared by adding 1.0 M NaOH to an equal volume of 2.0 M sodium bisulfite and stored frozen at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

Globins Scavenge Sulfur Trioxide Anion Radical

Gardner

2015

Journal of Biological Chemistry

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Background: Sulfite, an intermediate in sulfur metabolism, can be oxidized to the potentially toxic sulfur trioxide anion radical (STAR). Results: Diverse globins efficiently reduced STAR in vitro, and flavohemoglobin protected yeast from STAR toxicity. Conclusion: Globins can function as STAR scavengers. Significance: The data suggest roles for diverse globins in protecting cells against sulfite stress.

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“…In this mechanism, ferric Hb (methemoglobin) is reduced by ascorbate and the formed monodehydroascorbate (ascorbate free radical) is immediately scavenged by MDHAR. Low turnover rate of reaction in the presence of ascorbate and absence of MDHAR (apparently 0.03 s 21 heme 21 , calculated from the rate of heme reduction by ascorbate, Igamberdiev, unpublished), which is one order of magnitude higher than with NADH but one order of magnitude lower than for cytoglobin (26), demonstrates that the removal of monodehydroascorbate from the proximity of the heme constitutes the rate-limiting step and is crucial for NO scavenging that involves plant Hb. The NO scavenging system that involves non-symbiotic plant Hb differs strongly from other NO scavenging reactions (Table 2).…”

Section: Catalytic Cyclementioning

confidence: 99%

“…It could function at high NO/oxygen ratios but usually the NO dioxygenase reaction is inhibited under these conditions (for cytoglobin more than 1:500 (26) and for flavohemoglobins more than 1:100 (27)) arguing against the denitrosylase mechanism. The HbNO complex is inactive in the case of flavohemoglobins (27), and it is also inactive for cytoglobin that follows from NO inhibition (26), and, in the same manner, it is likely to be inactive in plant hemoglobins. There is no evidence to indicate whether NO dioxygenase activity associated with plant Hbs can be inhibited by increased NO/O 2 ratio but if this happens, it may actually be a limiting factor for NO scavenging in plants.…”

Section: Binding Of Ligandsmentioning

confidence: 99%

Structural and functional properties of class 1 plant hemoglobins

2011

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Nonsymbiotic class 1 plant hemoglobins are induced under hypoxia. Structurally they are protein dimers consisting of two identical subunits, each containing heme iron in a weak hexacoordinate state. The weak hexacoordination of heme‐iron binding to the distal histidine results in an extremely high avidity to oxygen, with a dissociation constant in the nanomolar range. This low dissociation constant is due to rapid oxygen binding resulting in protein conformational changes that slow dissociation from the heme site. Class 1 hemoglobins are characterized by an increased rate of Fe3+ reduction which is likely mediated by cysteine residue. This cysteine can form a reversible covalent bond between two monomers as shown by mass spectrometry analysis and, in addition to its structural role, prevents the molecule from autoxidation. The structural properties of class 1 hemoglobins allow them to serve as soluble electron transport proteins in the enzymatic system scavenging nitric oxide produced in low oxygen via reduction of nitrite. During oxygenation of nitric oxide to nitrate, oxidized ferric hemoglobin is formed (methemoglobin), which can be reduced by an associated reductase. The identified candidate for this reduction is monodehydroascorbate reductase. It is suggested that hemoglobin functions as a terminal electron acceptor during the hypoxic turnover of nitrogen, the process aided by its extremely high affinity for oxygen. © 2011 IUBMB IUBMB Life, 63(3): 146–152, 2011

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Nitric-oxide Dioxygenase Function of Human Cytoglobin with Cellular Reductants and in Rat Hepatocytes

Cited by 88 publications

References 65 publications

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

Globins Scavenge Sulfur Trioxide Anion Radical

Structural and functional properties of class 1 plant hemoglobins

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