Red blood cell membrane-facilitated release of nitrite-derived nitric oxide bioactivity

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

Research output: Contribution to journalArticle

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+ 虠 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.

Original languageEnglish (US)
Pages (from-to)6712-6723
Number of pages12
JournalBiochemistry®
Volume54
Issue number44
DOIs
StatePublished - Nov 10 2015
Externally publishedYes

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Cell membranes
Nitrites
Bioactivity
Nitric Oxide
Blood
Erythrocytes
Cell Membrane
Membranes
Scavenging
Blood Vessels
Dilatation
Hemoglobins
Cells
deoxyhemoglobin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Salgado, M. T., Cao, Z., Enika, N., Mohanty, J. G., & Rifkind, J. M. (2015). Red blood cell membrane-facilitated release of nitrite-derived nitric oxide bioactivity. Biochemistry®, 54(44), 6712-6723. https://doi.org/10.1021/acs.biochem.5b00643

Red blood cell membrane-facilitated release of nitrite-derived nitric oxide bioactivity. / Salgado, Maria T.; Cao, Zeling; Enika, Nagababu; Mohanty, Joy G.; Rifkind, Joseph M.

In: Biochemistry®, Vol. 54, No. 44, 10.11.2015, p. 6712-6723.

Research output: Contribution to journalArticle

Salgado, MT, Cao, Z, Enika, N, Mohanty, JG & Rifkind, JM 2015, 'Red blood cell membrane-facilitated release of nitrite-derived nitric oxide bioactivity', Biochemistry®, vol. 54, no. 44, pp. 6712-6723. https://doi.org/10.1021/acs.biochem.5b00643
Salgado, Maria T. ; Cao, Zeling ; Enika, Nagababu ; Mohanty, Joy G. ; Rifkind, Joseph M. / Red blood cell membrane-facilitated release of nitrite-derived nitric oxide bioactivity. In: Biochemistry®. 2015 ; Vol. 54, No. 44. pp. 6712-6723.
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