Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies

Chevalier, Alain; Guillochon, Didier; Nedjar, Naima; Piot, Jean Marie; Vijayalakshmi, Mokambes Waran; Thomas, Daniel

doi:10.1139/o90-119

Cited by 25 publications

(11 citation statements)

References 35 publications

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“…This result is in keeping with other studies indicating that the HBOCs have enhanced rates of transition to MetHb and ferryl heme upon exposure to H 2 O 2 (15,21). The faster rates of HBOC interaction with nitrite are also consistent with the concept that conformational constraints induced by cross-linking result in more solvent-accessible heme pockets (21,22).…”

Section: Nitrite-induced Oxidation Of Hbs In Aerobic Solutionssupporting

confidence: 91%

“…The rapid autoxidation of the HBOCs appears to be due to conformational constraints that make their heme pockets more open to the aqueous environment. Structural data supporting this interpretation has been acquired for glutaraldehyde-polymerized Hb (22,44). This cross-linked protein's enhanced rate of autoxidation is attributed to changes in the heme environment that decrease proximal and distal side steric hindrance and open the heme pocket toward the solvent (22).…”

Section: Discussionmentioning

confidence: 82%

“…Structural data supporting this interpretation has been acquired for glutaraldehyde-polymerized Hb (22,44). This cross-linked protein's enhanced rate of autoxidation is attributed to changes in the heme environment that decrease proximal and distal side steric hindrance and open the heme pocket toward the solvent (22). Low oxygen affinity need not be coupled to enhanced autoxidation and oxidative toxicity.…”

Section: Discussionmentioning

confidence: 87%

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Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins

et al. 2007

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SummaryA review of the oxidative and nitrosative reactions of cell-free hemoglobin-based oxygen carriers (HBOCs) shows that these reactions are intimately linked and are subject to allosteric control. Cross-linking reactions used to produce HBOCs introduce conformational constraints and result in Hbs with reduced responses to heterotropic and homotropic allosteric effectors. The Nernst plots of heme oxidation of cross-linked HBOCs are shifted to higher potentials relative to unmodified Hb in the absence of allosteric effectors, in accord with their T-state stabilization and right-shifted Hill plots of O 2 binding. They exhibit enhanced rates of autoxidation and nitrite-induced oxidation, features that appear due to their having more solvent-accessible heme pockets. The stability of their NO-Hb derivatives varies as a result of allosteric effects on the extent of formation of pentacoordinate NO-heme geometry by a chains and subsequent oxidation of partner b chains. The physiological implications of these findings on the safety, efficacy and design of second generation HBOCs are discussed in the framework of a reaction scheme showing linkages between Hbmediated redox reactions. These redox reactions can drive formation of SNO-Hb and other reactive species and are of significance for the use of cell-free Hbs in vivo.

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Section: Nitrite-induced Oxidation Of Hbs In Aerobic Solutionssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 87%

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Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins

et al. 2007

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“…However, their observed behavior is in keeping with previous studies indicating that these T-state stabilized Hbs have enhanced rates of transition to metHb and ferryl heme on exposure to H 2 O 2 (5,79,81). Their faster rates of interaction with nitrite are also consistent with data suggesting that the conformational constraints induced by cross-linking result in more solvent-accessible heme pockets (5,35). The results in Table 1 also show that inorganic anions and inositol hexaphosphate (IHP), effectors that lower Hb's O 2 affinity, exert opposite effects on the rate of nitrite-induced oxidation.…”

Section: Redox Reactions Of Hb With Nitritesupporting

confidence: 89%

Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

Bonaventura

Henkens

Alayash

et al. 2013

Antioxidants & Redox Signaling

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Significance: The broad classes of O 2 -binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O 2 -binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hbmediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298-2313. General PrinciplesEmergence of proteins capable of transporting O 2 I n this review, we examine the adaptive changes in the molecular controls of hemoglobin (Hb) oxygenation and oxidation that have evolved to meet the highly varied physiological and environmental demands of respiring organisms. Globins came into being during the planet's long early period of anoxia/hypoxia, and recent studies show that globins are either expressed or inducible in almost all cells (98). Studies have shown that one evolutionary pathway of Hb is that of a multipurpose domain attached to a variety of unrelated proteins, thus forming molecules with different functions (126). This pathway has allowed structurally distinct Hbs to evolve: (i) to protect against the high levels of nitrosative stress of the earth's early environment; (ii) to protect against O 2 -linked oxidation; (iii) to act as O 2 sensors that help regulate the expression of proteins during periods of hypoxia or anoxia; and (iv) to enable aerobic respiration by facilitating diffusion and/or acting as O 2 carriers (44,56,57,70,71,73,107). A common theme in the fascinating story of Hb evolution is the emergence of distinct mechanisms for controlling Hb's oxygenation and redox functions.Since increased amounts of O 2 were released in our planet's early history, O 2 toxicity brought about species extinction on a global scale. On the other hand, this ''oxygen pollution'' made possible a new biological process, that of aerobic respiration. A tremendous gain in the energy obtainable from oxidation of energy-rich metabolites was achieved when organisms evolve...

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“…This is consistent with a Mossbauer spectroscopic study of hemoglobin that showed that the heme pocket is opened up hy polymerization [16]. As a result, polymerized hemoglobins may be more susceptible to oxidation and heme loss.…”

Section: Resultssupporting

confidence: 89%

A Comparison of Rates of Heme Exchange: Site-Specifically Cross-Linked Versus Polymerized Human Hemoglobins

Vandegriff¹,

Le-Tellier²

1993

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Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies

Cited by 25 publications

References 35 publications

Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins

Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins

Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

A Comparison of Rates of Heme Exchange: Site-Specifically Cross-Linked Versus Polymerized Human Hemoglobins

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