Endothelial alpha globin is a nitrite reductase.

Autor: Keller TCS 4th; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA., Lechauve C; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA., Keller AS; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA., Broseghini-Filho GB; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil., Butcher JT; Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, USA., Askew Page HR; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., Islam A; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., Tan ZY; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., DeLalio LJ; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA., Brooks S; Physiology Unit, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Sharma P; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Hong K; Department of Physical Education, College of Education, Chung-Ang University, Seoul, South Korea., Xu W; Transgenic Mouse Facility, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA., Padilha AS; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil., Ruddiman CA; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA., Best AK; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., Macal E; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., Kim-Shapiro DB; Department of Physics, Translational Science Center, Wake Forest University, Winston-Salem, NC, USA., Christ G; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Yan Z; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA., Cortese-Krott MM; Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany., Ricart K; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Patel R; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Bender TP; Department of Microbiology, Immunology and Cancer, University of Virginia School of Medicine, Charlottesville, VA, USA., Sonkusare SK; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA., Weiss MJ; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA., Ackerman H; Physiology Unit, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Columbus L; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA.; Department of Chemistry, University of Virginia, Charlottesville, VA, USA., Isakson BE; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA. brant@virginia.edu.; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA. brant@virginia.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 27; Vol. 13 (1), pp. 6405. Date of Electronic Publication: 2022 Oct 27.
DOI: 10.1038/s41467-022-34154-3
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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