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Endothelial alpha globin is a nitrite reductase

Author

Listed:
  • T. C. Stevenson Keller

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Christophe Lechauve

    (St. Jude Children’s Research Hospital)

  • Alexander S. Keller

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Gilson Brás Broseghini-Filho

    (University of Virginia School of Medicine
    Federal University of Espirito Santo)

  • Joshua T. Butcher

    (Oklahoma State University)

  • Henry R. Askew Page

    (University of Virginia School of Medicine)

  • Aditi Islam

    (University of Virginia School of Medicine)

  • Zhe Yin Tan

    (University of Virginia School of Medicine)

  • Leon J. DeLalio

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Steven Brooks

    (National Institute of Allergy and Infectious Diseases)

  • Poonam Sharma

    (University of Virginia)

  • Kwangseok Hong

    (Chung-Ang University)

  • Wenhao Xu

    (University of Virginia School of Medicine)

  • Alessandra Simão Padilha

    (Federal University of Espirito Santo)

  • Claire A. Ruddiman

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Angela K. Best

    (University of Virginia School of Medicine)

  • Edgar Macal

    (University of Virginia School of Medicine)

  • Daniel B. Kim-Shapiro

    (Wake Forest University)

  • George Christ

    (University of Virginia)

  • Zhen Yan

    (University of Virginia School of Medicine)

  • Miriam M. Cortese-Krott

    (Heinrich Heine University)

  • Karina Ricart

    (University of Alabama at Birmingham)

  • Rakesh Patel

    (University of Alabama at Birmingham)

  • Timothy P. Bender

    (University of Virginia School of Medicine)

  • Swapnil K. Sonkusare

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Mitchell J. Weiss

    (St. Jude Children’s Research Hospital)

  • Hans Ackerman

    (National Institute of Allergy and Infectious Diseases)

  • Linda Columbus

    (University of Virginia School of Medicine
    University of Virginia)

  • Brant E. Isakson

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

Abstract

Resistance artery vasodilation in response to hypoxia is essential for matching tissue oxygen and demand. In hypoxia, erythrocytic hemoglobin tetramers produce nitric oxide through nitrite reduction. We hypothesized that the alpha subunit of hemoglobin expressed in endothelium also facilitates nitrite reduction proximal to smooth muscle. Here, we create two mouse strains to test this: an endothelial-specific alpha globin knockout (EC Hba1Δ/Δ) and another with an alpha globin allele mutated to prevent alpha globin’s inhibitory interaction with endothelial nitric oxide synthase (Hba1WT/Δ36–39). The EC Hba1Δ/Δ mice had significantly decreased exercise capacity and intracellular nitrite consumption in hypoxic conditions, an effect absent in Hba1WT/Δ36–39 mice. Hypoxia-induced vasodilation is significantly decreased in arteries from EC Hba1Δ/Δ, but not Hba1WT/Δ36–39 mice. Hypoxia also does not lower blood pressure in EC Hba1Δ/Δ mice. We conclude the presence of alpha globin in resistance artery endothelium acts as a nitrite reductase providing local nitric oxide in response to hypoxia.

Suggested Citation

  • T. C. Stevenson Keller & Christophe Lechauve & Alexander S. Keller & Gilson Brás Broseghini-Filho & Joshua T. Butcher & Henry R. Askew Page & Aditi Islam & Zhe Yin Tan & Leon J. DeLalio & Steven Brook, 2022. "Endothelial alpha globin is a nitrite reductase," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34154-3
    DOI: 10.1038/s41467-022-34154-3
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    References listed on IDEAS

    as
    1. John R. Pawloski & Douglas T. Hess & Jonathan S. Stamler, 2001. "Export by red blood cells of nitric oxide bioactivity," Nature, Nature, vol. 409(6820), pages 622-626, February.
    2. Rhianna C. Laker & Joshua C. Drake & Rebecca J. Wilson & Vitor A. Lira & Bevan M. Lewellen & Karen A. Ryall & Carleigh C. Fisher & Mei Zhang & Jeffrey J. Saucerman & Laurie J. Goodyear & Mondira Kundu, 2017. "Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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    Cited by:

    1. Alejandro Moreno-Domínguez & Olalla Colinas & Ignacio Arias-Mayenco & José M. Cabeza & Juan L. López-Ogayar & Navdeep S. Chandel & Norbert Weissmann & Natascha Sommer & Alberto Pascual & José López-Ba, 2024. "Hif1α-dependent mitochondrial acute O2 sensing and signaling to myocyte Ca2+ channels mediate arterial hypoxic vasodilation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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