Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia
Abstract
Oxygen delivery by RBC Hb is essential for life. Just three amino acids in Hb are conserved in all mammals and birds, but only two of those are required to carry oxygen. The third, a Cys within the β-chain, βCys93, has been assigned a role in carrying nitric oxide, which mediates vasodilation. However, the physiological importance of RBC-mediated vasoregulation is unknown. We show that blood flow and tissue oxygenation are markedly impaired in mice with a βCys93Ala mutation. The βCys93Ala mutation also results in myocardial ischemia, cardiac decompensation, and enhanced mortality. These findings support a new view of the respiratory cycle wherein, remarkably, RBCs regulate blood flow and (βCys93NO)-Hb is necessary for adequate tissue oxygenation and normal cardiovascular function.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 25, 2015
- Source ID
- 10.1073/pnas.1502285112
Entities
People
- Alfred Hausladen
- Douglas T. Hess
- Fabio Fonseca
- James D. Reynolds
- Jonathan S. Stamler
- Rongli Zhang
- Ruchi Chaube
- Zhaoxia Qian
Organizations
- Case Western Reserve University
- National Heart, Lung, and Blood Institute
- UH Cleveland Medical Center