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Endothelial alpha globin is a nitrite reductase.
Keller, T C Stevenson; Lechauve, Christophe; Keller, Alexander S; Broseghini-Filho, Gilson Brás; Butcher, Joshua T; Askew Page, Henry R; Islam, Aditi; Tan, Zhe Yin; DeLalio, Leon J; Brooks, Steven; Sharma, Poonam; Hong, Kwangseok; Xu, Wenhao; Padilha, Alessandra Simão; Ruddiman, Claire A; Best, Angela K; Macal, Edgar; Kim-Shapiro, Daniel B; Christ, George; Yan, Zhen; Cortese-Krott, Miriam M; Ricart, Karina; Patel, Rakesh; Bender, Timothy P; Sonkusare, Swapnil K; Weiss, Mitchell J; Ackerman, Hans; Columbus, Linda; Isakson, Brant E.
Afiliación
  • Keller TCS; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Lechauve C; Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Keller AS; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Broseghini-Filho GB; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Butcher JT; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Askew Page HR; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Islam A; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil.
  • Tan ZY; Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, USA.
  • DeLalio LJ; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Brooks S; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Sharma P; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Hong K; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Xu W; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Padilha AS; Physiology Unit, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
  • Ruddiman CA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
  • Best AK; Department of Physical Education, College of Education, Chung-Ang University, Seoul, South Korea.
  • Macal E; Transgenic Mouse Facility, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Kim-Shapiro DB; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil.
  • Christ G; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Yan Z; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Cortese-Krott MM; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Ricart K; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Patel R; Department of Physics, Translational Science Center, Wake Forest University, Winston-Salem, NC, USA.
  • Bender TP; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
  • Sonkusare SK; Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Weiss MJ; Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
  • Ackerman H; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Columbus L; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Isakson BE; Department of Microbiology, Immunology and Cancer, University of Virginia School of Medicine, Charlottesville, VA, USA.
Nat Commun ; 13(1): 6405, 2022 10 27.
Article en En | MEDLINE | ID: mdl-36302779
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido Nítrico / Nitrito Reductasas Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Óxido Nítrico / Nitrito Reductasas Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos