ArticleProceedings of the National Academy of Sciences of the United States of America2015
Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- Red Blood Cells in Normal and Pathological States: Redox Reactions of Hemoglobin.Molecules (Basel, Switzerland) · 2026Review
- Emerging concepts in the molecular cell biology and functions of mammalian erythrocytes.The Journal of biological chemistry · 2025Review
- Erythrocytes enhance oxygen-carrying capacity through self-regulation.Frontiers in physiology · 2025Review
- The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.International journal of molecular sciences · 2024Review
- Endothelial LAT1 (SLC7A5) Mediates S-Nitrosothiol Import and Modulates Respiratory Sequelae of Red Blood Cell Transfusion In Vivo.Thrombosis and haemostasis · 2024Article
- Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.International journal of molecular sciences · 2024Review
- Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.Frontiers in physiology · 2024Review
- Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.Heliyon · 2023Review
- Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent andJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Control of tissue oxygenation by S-nitrosohemoglobin in human subjects.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- S-Nitroso-l-cysteine and ventilatory drive: A pediatric perspective.Pediatric pulmonology · 2022Review
- S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- A physiologically relevant role for NO stored in vascular smooth muscle cells: A novel theory of vascular NO signaling.Redox biology · 2022Review
- Optimized S-nitrosohemoglobin Synthesis in Red Blood Cells to Preserve Hypoxic Vasodilation ViaThe Journal of pharmacology and experimental therapeutics · 2022Article
- Inhaled nitric oxide: role in the pathophysiology of cardio-cerebrovascular and respiratory diseases.Intensive care medicine experimental · 2022Review
- Nitric Oxide Production and Regulation in the Teleost Cardiovascular System.Antioxidants (Basel, Switzerland) · 2022Review
- S-Nitrosylated hemoglobin predicts organ yield in neurologically-deceased human donors.Scientific reports · 2022Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Article
- The enzymatic function of the honorary enzyme: S-nitrosylation of hemoglobin in physiology and medicine.Molecular aspects of medicine · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Oxygen delivery by Hb is essential for vertebrate life. Three amino acids in Hb are strictly conserved in all mammals and birds, but only two of those, a His and a Phe that stabilize the heme moiety, are needed to carry O2. The third conserved residue is a Cys within the β-chain (βCys93) that has been assigned a role in S-nitrosothiol (SNO)-based hypoxic vasodilation by RBCs. Under this model, the delivery of SNO-based NO bioactivity by Hb redefines the respiratory cycle as a triune system (NO/O2/CO2). However, the physiological ramifications of RBC-mediated vasodilation are unknown, and the apparently essential nature of βCys93 remains unclear. Here we report that mice with a βCys93Ala mutation are deficient in hypoxic vasodilation that governs blood flow autoregulation, the classic physiological mechanism that controls tissue oxygenation but whose molecular basis has been a longstanding mystery. Peripheral blood flow and tissue oxygenation are decreased at baseline in mutant animals and decline excessively during hypoxia. In addition, βCys93Ala mutation results in myocardial ischemia under basal normoxic conditions and in acute cardiac decompensation and enhanced mortality during transient hypoxia. Fetal viability is diminished also. Thus, βCys93-derived SNO bioactivity is essential for tissue oxygenation by RBCs within the respiratory cycle that is required for both normal cardiovascular function and circulatory adaptation to hypoxia.
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