ArticleThe Journal of biological chemistry2011
14-3-3 binding and phosphorylation of neuroglobin during hypoxia modulate six-to-five heme pocket coordination and rate of nitrite reduction to nitric oxide.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 72 citations in OpenAlex.
- Neuroglobin: A New Player in the Gut-Brain Axis.International journal of molecular sciences · 2026Review
- Therapeutic Potential of Cytoglobin and Neuroglobin in Oxidative Stress-Driven Liver Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Cytoprotective Action of Sodium Fumarate in anSovremennye tekhnologii v meditsine · 2025Article
- Ligand-Based Regulation of Dynamics and Reactivity of Hemoproteins.Biomolecules · 2023Review
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Neuroglobin and neuroprotection: the role of natural and synthetic compounds in neuroglobin pharmacological induction.Neural regeneration research · 2021Review
- Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection.Cells · 2021Review
- Biological Mechanisms ofAntioxidants (Basel, Switzerland) · 2021Review
- Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport.Redox biology · 2020Review
- Regulation of Nitric Oxide Metabolism and Vascular Tone by Cytoglobin.Antioxidants & redox signaling · 2020Review
- Nitrite Improves Heart Regeneration in Zebrafish.Antioxidants & redox signaling · 2020Article
- Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy.Antioxidants (Basel, Switzerland) · 2019Article
- Article
- Neuroglobin Expression in the Brain: a Story of Tissue Homeostasis Preservation.Molecular neurobiology · 2019Review
- Evidence for a Large Expansion and Subfunctionalization of Globin Genes in Sea Anemones.Genome biology and evolution · 2018Article
- Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1.International journal of molecular sciences · 2018Article
- Neuroglobin boosts axon regeneration during ischemic reperfusion via p38 binding and activation depending on oxygen signal.Cell death & disease · 2018Article
- Efficient Reduction of Vertebrate Cytoglobins by the Cytochrome bBiochemistry · 2017Article
- Neuroglobin Can Prevent or Reverse Glaucomatous Progression in DBA/2J Mice.Molecular therapy. Methods & clinical development · 2017Article
- Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Neuroglobin protects neurons from hypoxia in vitro and in vivo; however, the underlying mechanisms for this effect remain poorly understood. Most of the neuroglobin is present in a hexacoordinate state with proximal and distal histidines in the heme pocket directly bound to the heme iron. At equilibrium, the concentration of the five-coordinate neuroglobin remains very low (0.1-5%). Recent studies have shown that post-translational redox regulation of neuroglobin surface thiol disulfide formation increases the open probability of the heme pocket and allows nitrite binding and reaction to form NO. We hypothesized that the equilibrium between the six- and five-coordinate states and secondary reactions with nitrite to form NO could be regulated by other hypoxia-dependent post-translational modification(s). Protein sequence models identified candidate sites for both 14-3-3 binding and phosphorylation. In both in vitro experiments and human SH-SY5Y neuronal cells exposed to hypoxia and glucose deprivation, we observed that 1) neuroglobin phosphorylation and protein-protein interactions with 14-3-3 increase during hypoxic and metabolic stress; 2) neuroglobin binding to 14-3-3 stabilizes and increases the half-life of phosphorylation; and 3) phosphorylation increases the open probability of the heme pocket, which increases ligand binding (CO and nitrite) and accelerates the rate of anaerobic nitrite reduction to form NO. These data reveal a series of hypoxia-dependent post-translational modifications to neuroglobin that regulate the six-to-five heme pocket equilibrium and heme access to ligands. Hypoxia-regulated reactions of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia.
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