pr6b00733_si_002.xlsx (2.29 MB)
Download fileAltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia
dataset
posted on 2016-09-20, 00:00 authored by Angelo D’Alessandro, Travis Nemkov, Kaiqi Sun, Hong Liu, Anren Song, Andrew
A. Monte, Andrew W. Subudhi, Andrew T. Lovering, Daniel Dvorkin, Colleen
G. Julian, Christopher G. Kevil, Gopi K. Kolluru, Sruti Shiva, Mark T. Gladwin, Yang Xia, Kirk C. Hansen, Robert C. RoachRed 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 (5260 m) for 1, 7, and 16 days, and following reascent
after 7 days at 1525 m. 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 >5000 m, 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 sulfur/H2S metabolism. Metabolic adaptations
were preserved 1 week after descent, consistently with improved physical
performances in comparison to the first ascendance, suggesting a mechanism
of metabolic memory.