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J Proteome Res. 2016 Oct 7;15(10):3883-3895. Epub 2016 Sep 27.

AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia.

Author information

1
Department of Biochemistry and Molecular Genetics, University of Colorado Denver , Anschutz Medical Campus, Aurora, Colorado 80045, United States.
2
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston , Houston, Texas, United States.
3
Altitude Research Center, Department of Emergency Medicine, University of Colorado , Anschutz Medical Campus, Aurora, Colorado, United States.
4
Department of Biology, University of Colorado Colorado Springs , Colorado Springs, Colorado, United States.
5
Department of Human Physiology, University of Oregon , Eugene, Oregon, United States.
6
Department of Pathology, Centre for Cardiovascular Diseases and Sciences, LSU Health , Shreveport, Louisiana, United States.
7
Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania, United States.

Abstract

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 (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.

KEYWORDS:

hydrogen sulfide; mass spectrometry; metabolic linkage; metabolomics; nitric oxide; red blood cell

PMID:
27646145
PMCID:
PMC5512539
DOI:
10.1021/acs.jproteome.6b00733
[Indexed for MEDLINE]
Free PMC Article

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