ArticleNitric oxide : biology and chemistry2011
Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling.
Article in Nitric oxide : biology and chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Nitrosyl hemoglobin formation from nitrite in normal and sickle blood.Free radical biology & medicine · 2024Article
- Nitric Oxide Signaling Pathway in Ventral Tegmental Area is Involved in Regulation of 7,8-Dihydroxyflavone on Alcohol Consumption in Rats.Molecular neurobiology · 2022Article
- The role of nitric oxide in brain disorders: Autism spectrum disorder and other psychiatric, neurological, and neurodegenerative disorders.Redox biology · 2020Review
- Glutaraldehyde cross-linking increases the stability of Lumbricus terrestris erythrocruorin.Biotechnology progress · 2018Article
- Increasing the stability of Lumbricus terrestris erythrocruorin via poly(acrylic acid) conjugation.Artificial cells, nanomedicine, and biotechnology · 2018Article
- HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.Antioxidants & redox signaling · 2017Review
- A mathematical model for the role of NNitric oxide : biology and chemistry · 2016Article
- Overview of Antagonists Used for Determining the Mechanisms of Action Employed by Potential Vasodilators with Their Suggested Signaling Pathways.Molecules (Basel, Switzerland) · 2016Review
- Evaluating the capacity to generate and preserve nitric oxide bioactivity in highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with potential blood substitute properties.The Journal of biological chemistry · 2015Article
- Role of nitrite in regulation of fetal cephalic circulation in sheep.The Journal of physiology · 2014Article
- The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions.PloS one · 2014Article
- Effects of erythrocyte aging on nitric oxide and nitrite metabolism.Antioxidants & redox signaling · 2013Article
- Generating S-nitrosothiols from hemoglobin: mechanisms, conformational dependence, and physiological relevance.The Journal of biological chemistry · 2013Article
- Antioxidant functions for the hemoglobin β93 cysteine residue in erythrocytes and in the vascular compartment in vivo.Free radical biology & medicine · 2013Article
- Nitric oxide formation versus scavenging: the red blood cell balancing act.The Journal of physiology · 2012Review
- Oxygen regulates tissue nitrite metabolism.Antioxidants & redox signaling · 2012Article
- Erythrocyte storage increases rates of NO and nitrite scavenging: implications for transfusion-related toxicity.The Biochemical journal · 2012Article
- Inhalation of NO during myocardial ischemia reduces infarct size and improves cardiac function.Intensive care medicine · 2012Article
- Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.Nitric oxide : biology and chemistry · 2012Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Recent data suggest that transitions between the relaxed (R) and tense (T) state of hemoglobin control the reduction of nitrite to nitric oxide (NO) by deoxyhemoglobin. This reaction may play a role in physiologic NO homeostasis and be a novel consideration for the development of the next generation of hemoglobin-based blood oxygen carriers (HBOCs, i.e. artificial blood substitutes). Herein we tested the effects of chemical stabilization of bovine hemoglobin in either the T- (THb) or R-state (RHb) on nitrite-reduction kinetics, NO-gas formation and ability to stimulate NO-dependent signaling. These studies were performed over a range of fractional saturations that is expected to mimic biological conditions. The initial rate for nitrite-reduction decreased in the following order RHb>bHb>THb, consistent with the hypothesis that the rate constant for nitrite reduction is faster with R-state Hb and slower with T-state Hb. Moreover, RHb produced more NO-gas and inhibited mitochondrial respiration more potently than both bHb and THb. Interestingly, at low oxygen fractional saturations, THb produced more NO and stimulated nitrite-dependent vasodilation more potently than bHb despite both derivatives having similar initial rates for nitrite reduction and a more negative reduction potential in THb versus bHb. These data suggest that cross-linking of bovine hemoglobin in the T-state conformation leads to a more effective coupling of nitrite reduction to NO-formation. Our results support the model of allosteric regulation of nitrite reduction by deoxyhemoglobin and show that cross-linking hemoglobins in distinct quaternary states can generate products with increased NO yields from nitrite reduction that could be harnessed to promote NO-signaling in vivo.
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