Reactivity Studies of the Fe(III) and Fe(II)NO Forms of Human Neuroglobin Reveal a Potential Role against Oxidative Stress

Herold, Susanna; Fago, Angela; Weber, Roy E.; Dewilde, Sylvia; Moëns, Luc

doi:10.1074/jbc.m313732200

Cited by 248 publications

(322 citation statements)

References 48 publications

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“…A major fate of NO produced during hypoxia is that it reacts with superoxide in the diffusion-limited reaction, forming peroxynitrite (ONOO 7 ), a potent oxidating and nitrating agent, whose role in cellular damage during brain hypoxia has been recognized (28). We have recently shown that in the Fe 2+ 7NO form Ngb reacts more rapidly with peroxynitrite than Hb does (29). This scavenging property may protect the neurons and contribute to their survival following hypoxic episodes.…”

Section: Neuroglobin As Scavenger Of Reactive Oxygen and Nitrogen Spementioning

confidence: 99%

“…This scavenging property may protect the neurons and contribute to their survival following hypoxic episodes. Additionally, in contrast to Hb and Mb, the reaction of met (Fe 3+ ) Ngb with peroxynitrite or hydrogen peroxide does not appear to generate the cytotoxic ferryl (Fe 4+ ) species, another feature that may contribute to cellular survival (29).…”

Section: Neuroglobin As Scavenger Of Reactive Oxygen and Nitrogen Spementioning

confidence: 99%

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Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins

et al. 2004

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SummaryNeuroglobin and cytoglobin are two recently discovered vertebrate globins, which are expressed at low levels in neuronal tissues and in all tissues investigated so far, respectively. Based on their amino acid sequences, these globins appear to be phylogenetically ancient and to have mutated less during evolution in comparison to the other vertebrate globins, myoglobin and hemoglobin. As with some plant and bacterial globins, neuroglobin and cytoglobin hemes are hexacoordinate in the absence of external ligands, in that the heme iron atom coordinates both a proximal and a distal His residue. While the physiological role of hexacoordinate globins is still largely unclear, neuroglobin appears to participate in the cellular defence against hypoxia. We present the current knowledge on the functional properties of neuroglobin and cytoglobin, and describe a mathematical model to evaluate the role of mammalian retinal neuroglobin in supplying O 2 supply to the mitochondria. As shown, the model argues against a significant such role for neuroglobin, that more likely plays a role to scavenge reactive oxygen and nitrogen species that are generated following brain hypoxia. The O 2 binding properties of cytoglobin, which is upregulated upon hypoxia, are consistent with a role for this protein in O 2 -requiring reactions, such as those catalysed by hydroxylases.

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Section: Neuroglobin As Scavenger Of Reactive Oxygen and Nitrogen Spementioning

confidence: 99%

Section: Neuroglobin As Scavenger Of Reactive Oxygen and Nitrogen Spementioning

confidence: 99%

Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins

et al. 2004

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“…In contrast with penta-coordinated globins (e.g., Hb and Mb) (28,(44)(45)(46)(47)(48)(49)(50)(51), heme-Fe(III) human Ngb apparently does not generate the heme-Fe(IV)¼ ¼O form when exposed to H 2 O 2 and peroxynitrite, another feature of Ngb that may contribute to neuronal survival after hypoxia and that may be related to heme-Fe-atom hexa-coordination (28,30,31).…”

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confidence: 99%

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

et al. 2008

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SummaryGlobins are generally considered as carriers of diatomic gaseous ligands (e.g., O 2 and NO) in metazoa. Recently, the (pseudo-)enzymatic activity of globins towards reactive nitrogen and oxygen species has been elucidated. In particular, some globins (e.g., hemoglobin and myoglobin) catalyze the enzymatic scavenging of NO and peroxynitrite in the presence of H 2 O 2 . Indeed, H 2 O 2 oxidizes some globins leading to the formation of water and of the heme-protein ferryl derivative, which, in turn, oxidizes NO and peroxynitrite leading to the formation of the globin ferric species, NO 2 2 , and NO 3 2 . Here, we hypothesize that NO, peroxynitrite, and H 2 O 2 are co-substrates for the peroxidase activity of some globins, this catalytic activity was reported in 1900 for the first time, even though the substrates have never been identified firmly up to now. The hemoglobin (Hb) superfamily includes several hemeproteins, generally referred to as globins, which are found in all kingdoms of living organisms (1, 2). Globin functions have been the subject of active debate, in addition to dioxygen transport and storage. Several functions have been proposed recently, including control of nitrogen monoxide levels, O 2 sensing, and dehaloperoxidase activity (3-15).Globins share physical, spectroscopic, and chemical similarities with peroxidases (16,17). In fact, as demonstrated first in 1900 (18), Hb reacts readily with hydrogen peroxide (H 2 O 2 ). In 1923, the peroxidase activity of Hb has been reported (19), and in 1938, the modulation of the peroxidase activity of Hb by haptoglobin has been demonstrated (20). The reaction of myoglobin (Mb) with H 2 O 2 , on the other hand, apparently was not considered until 1952 (21), and the ability of Mb to catalyze peroxide oxidation of substrates was not reported until 1955 (22). Upon reaction with H 2 O 2 , Mb and Hb form the cytotoxic ferryl derivative (heme-Fe(IV)¼ ¼O), which is similar to compound II formed by peroxidases (23, 24). Heme-Fe(IV)¼ ¼O is able to oxidize a wide range of reducing substrates, such as phenols and aromatic amines, even though substrate peroxidation by Hb and Mb is far less efficient than that of peroxidases (24, 25), ruling out the possibility that the potential peroxidase activity of Hb and Mb is exerted on this class of substrates under normal conditions.Here, we hypothesize that the capability of some globins (e.g., Hb and Mb) to form a compound II-like species under oxidative stress may be actually exploited to avoid the building up of NO and peroxynitrite, 1 which can be then identified as the 'true' substrates for the peroxidase activity of Hb and Mb.Heme-proteins share the ability of detoxifying nitrogen reactive species, for example, NO. Even though leukocyte peroxi- 1 The term peroxynitrite is used in the text to refer generically to both ONOO 2 and its conjugated acid HOONO (38).

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“…Although the exact role of hNgb in oxidative stress is still unclear, ROS scavenging ability has been suggested (35)(36)(37). Several in vitro experiments have suggested that Ngb is able to scavenge free radical (38,39). Moreover, Fordel et al observed that the intracellular H 2 O 2 level is negatively correlated with hNgb expression in eyes of mice in hypoxia/reoxygenation studies (40).…”

Section: Discussionmentioning

confidence: 99%

GLB‐13 is associated with oxidative stress resistance in caenorhabditis elegans

Ren

Han

et al. 2013

IUBMB Life

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Globins constitute a superfamily of heme-binding proteins that is widely present in many species. There are 33 putative globins in the genome of Caenorhabditis elegans, where glb-13 is a homolog of neuroglobin (Ngb) based on sequence analysis and specific expression in neurons. Here we examined whether glb-13 as well as Ngb is also associated with resistance to reactive oxygen species (ROS) induced by paraquat. Our results showed that the mRNA level of glb-13 was significantly upregulated after paraquat exposure. Expression of a green fluorescent protein (GFP) reporter gene directed by the glb-13 promoter was increased by paraquat exposure. The mutant C. elegans strain glb-13(tm2825) was sensitive to paraquat-induced oxidative stress. Overexpression of human Ngb (hNgb) in C. elegans neuronal cells can rescue the paraquat sensitive phenotype of the mutant strain. glb-13 mutation or hNgb overexpression did not affect the expression of antioxidant enzymes such as superoxide dismutase (SOD). To examine the ROS-scavenging capabilities of hNgb and glb-13, we further examined the level of ROS in glb-13 mutant and hNgb transgenic (hNgb-Tg) worms. There was no statistical difference in ROS levels in the untreated controls; however in paraquattreated worms, the ROS level was statistically repressed in the hNgb-Tg relative to enhanced green fluorescent protein (EGFP)-Tg worms or wildtype animals. Additionally, the ROS level of glb-13 mutant was statistically higher than the wildtype animals. Furthermore, hNgb overexpression diminished the ROS level of glb-13 mutant. In conclusion, hNgb can rescue the ROS sensitive phenotype of the glb-13 mutant strain. The protein GLB-13 seems to have an hNgb-like function, suggesting the importance of the globin protein family in maintaining the homeostasis of ROS signals. Our data provided evidence for the first time that glb-13 is associated with the resistance against oxidative stress-induced toxicity.

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Reactivity Studies of the Fe(III) and Fe(II)NO Forms of Human Neuroglobin Reveal a Potential Role against Oxidative Stress

Cited by 248 publications

References 48 publications

Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins

Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins

Catalytic peroxidation of nitrogen monoxide and peroxynitrite by globins

GLB‐13 is associated with oxidative stress resistance in caenorhabditis elegans

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