TY - JOUR
T1 - AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia
AU - d’Alessandro, Angelo
AU - Nemkov, Travis
AU - Sun, Kaiqi
AU - Liu, Hong
AU - Song, Anren
AU - Monte, Andrew A.
AU - Subudhi, Andrew W.
AU - Lovering, Andrew T.
AU - Dvorkin, Daniel
AU - Julian, Colleen G.
AU - Kevil, Christopher G.
AU - Kolluru, Gopi K.
AU - Shiva, Sruti
AU - Gladwin, Mark T.
AU - Xia, Yang
AU - Hansen, Kirk C.
AU - Roach, Robert C.
N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.jproteome.6b00733
PY - 2016/10/7
Y1 - 2016/10/7
N2 - Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated.
Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters.
Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism.
Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic
memory.
AB - Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated.
Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters.
Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism.
Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic
memory.
UR - http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.6b00733
U2 - 10.1021/acs.jproteome.6b00733
DO - 10.1021/acs.jproteome.6b00733
M3 - Article
SN - 1535-3893
VL - 15
SP - 3883
EP - 3895
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 10
ER -