Cited by 34Hemoglobin structure and functionNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

Red Blood Cell Membrane-Facilitated Release of Nitrite-Derived Nitric Oxide Bioactivity

Salgado, Maria T., Cao, Zeling, Nagababu, Enika, Mohanty, Joy G., Rifkind, Joseph M.·2015·Biochemistry

Abstract

The reduction of nitrite by deoxyhemoglobin to nitric oxide (NO) has been proposed as a mechanism for the transfer of NO bioactivity from the red blood cell (RBC) to the vasculature. This transfer can increase vascular dilatation. The major challenge to this hypothesis is the very efficient scavenging of NO by hemoglobin, which prevents the release of NO from RBCs. Previous studies indicate that the reaction of nitrite with deoxyhemoglobin produces two metastable intermediates involving nitrite bound to deoxyhemoglobin and a hybrid intermediate [Hb(II)NO(+) ↔ Hb(III)NO] where the nitrite is reduced, but unavailable to react with hemoglobin. We have now shown how unique properties of these intermediates provide a pathway for the release of NO bioactivity from RBCs. The high membrane affinity of these intermediates (>100-fold greater than that of deoxyhemoglobin) places these intermediates on the membrane. Furthermore, membrane-induced conformational changes of the nitrite-reacted intermediates facilitate the release of NO from the hybrid intermediate and nitrite from the nitrite-bound intermediate. Increased membrane affinity, coupled with facilitated dissociation of NO and nitrite from the membrane-bound intermediates, provides the first realistic mechanism for the potential release of NO and nitrite from the RBC and their potential transfer to the vasculature.

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Crossref · 10.1021/acs.biochem.5b00643

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  • Red blood cells play a pivotal role in facilitating nitrite reduction via deoxyhaemoglobin, especially in hypoxic and acidic conditions, enabling targeted delivery of NO to oxygen-deprived tissues.

    “Red blood cells (RBCs) play a pivotal role in facilitating nitrite reduction via deoxyhaemoglobin, especially in hypoxic and acidic conditions. This enables the targeted delivery of NO to oxygen-deprived tissues [82].”
  • Beetroot is one of the richest dietary sources of inorganic nitrate (250-400 mg/100 g fresh weight), depending on agronomic and storage conditions.

    “Depending on agronomic and storage conditions, it is also one of the richest dietary sources of inorganic nitrate (250–400 mg/100 g fresh weight) [80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95].”

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Authors
Salgado, M. T., Cao, Z., Nagababu, E., Mohanty, J. G., & Rifkind, J. M.
Affiliations
National Institutes of Health (US)
Corresponding author
Rifkind, Joseph M.
Venue
Biochemistry
Published
2015-10-28
Volume
54
Issue
44
Pages
6712-6723
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2433011679
Cited by
34
References
41
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 7
FWCI
3.02
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
nitric oxide release, nitrite, deoxyhemoglobin, erythrocyte membrane, nitrite reduction, membrane affinity, conformational change, vascular system, vascular dilation
MeSH terms
Erythrocyte Membrane, Hemoglobins, Humans, Nitric Oxide, Nitrites, Oxidation-Reduction

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