Reactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditions
Abstract
Recent evidence suggests that the reaction of nitrite with deoxygenated hemoglobin and myoglobin contributes to the generation of nitric oxide and S-nitrosothiols in vivo under conditions of low oxygen availability. We have investigated whether ferrous neuroglobin and cytoglobin, the two hexacoordinate globins from vertebrates expressed in brain and in a variety of tissues, respectively, also react with nitrite under anaerobic conditions. Using absorption spectroscopy, we find that ferrous neuroglobin and nitrite react with a second-order rate constant similar to that of myoglobin, whereas the ferrous heme of cytoglobin does not react with nitrite. Deconvolution of absorbance spectra shows that, in the course of the reaction of neuroglobin with nitrite, ferric Fe(III) heme is generated in excess of nitrosyl Fe(II)-NO heme as due to the low affinity of ferrous neuroglobin for nitric oxide. By using ferrous myoglobin as scavenger for nitric oxide, we find that nitric oxide dissociates from ferrous neuroglobin much faster than previously appreciated, consistently with the decay of the Fe(II)-NO product during the reaction. Both neuroglobin and cytoglobin are S-nitrosated when reacting with nitrite, with neuroglobin showing higher levels of S-nitrosation. The possible biological significance of the reaction between nitrite and neuroglobin in vivo under brain hypoxia is discussed.
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8 mmol potassium nitrate did not significantly affect FMD, but significantly reduced pulse wave velocity (0.3 m/s) and systolic BP (4 mmHg) at 3 h compared with potassium chloride control in fourteen healthy subjects.
“However, Bahra et al. (87) did not find a significant effect of 8 mmol potassium nitrate on FMD, but reported a significant reduction (0•3 m/s) in pulse wave velocity and SBP (4 mmHg) at 3 h compared with the potassium chloride control in fourteen healthy subjects.”
From The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies (2013) · cites this paper as [87]
In healthy normotensive subjects, acute dietary nitrate from beetroot juice and inorganic salts has a dose-dependent effect on peak change in systolic blood pressure (R2=0.45, P=0.033).
“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
From The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies (2013) · cites this paper as [87]
In healthy normotensive subjects, acute dietary nitrate from beetroot juice and inorganic salts does not have a significant dose-dependent effect on peak change in diastolic blood pressure (R2=0.27, P=0.233).
“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
From The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies (2013) · cites this paper as [87]
Nitrite reduction is not exclusive to hemoglobin and myoglobin; a variety of heme-containing and non-heme containing proteins have been suggested as mediators of NO formation.
“Nitrite reduction is not exclusive to hemoglobin and myoglobin, with a variety of heme-containing and non-heme containing proteins including xanthine oxidoreductase [21, 22], aldehyde oxidase [62], neuroglobin [63, 64], eNOS [65], cytochrome c [47], carbonic anhydrase [66], cytochrome c oxidase [67], complex III [68], and cytochrome P450 [69] being suggested as mediators of NO-formation.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [63]
The nitrite reductase activity of neuroglobin or cytochrome c is negligible when the heme is hexacoordinated.
“the nitrite reductase activity of neuroglobin [63, 64, 70, 76] or cytochrome c [47] is negligible when the heme is hexacoordinated.”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [63]
Neuroglobin and cytoglobin may also facilitate nitrite reduction.
“Moreover, recent reports also demonstrate that neuroglobin and cytoglobin may also facilitate nitrite reduction [39, 115].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [115]
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References 56 · Cited by 144
- Authors
- Petersen, M. G., Dewilde, S., & Fago, A.
- Affiliations
- Aarhus University (DK)
- University of Antwerp (BE)
- Corresponding author
- Fago, Angela
- ORCID
- Fago, Angela
- Venue
- Journal of Inorganic Biochemistry
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 102
- Issue
- 9
- Pages
- 1777-1782
- ISSN
- 0162-0134 (ISSN-L)
- OpenAlex
- W2083809966
- Cited by
- 144
- References
- 56
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 5 · 2018: 6 · 2017: 14 · 2016: 11 · 2015: 8 · 2014: 10 · 2013: 12 · 2012: 12
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Inorganic Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- neuroglobin, cytoglobin, nitrite, nitric oxide, S-nitrosylation, S-nitrosothiols, heme iron oxidation, nitric oxide dissociation, myoglobin, cerebral hypoxia, anaerobic conditions
- MeSH terms
- Neuroglobin, Cytoglobin, Anaerobiosis, Animals, Chromatography, Gel, Globins, Kinetics, Nerve Tissue Proteins, Nitrites
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