AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

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. Roach

doi:10.1021/acs.jproteome.6b00733

AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

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. Roach

University of Colorado Denver
University of Texas Health Science Center at Houston
University of Colorado, Aurora
University of Oregon
Louisiana State University Health Sciences Center
University of Pittsburgh
University of Colorado at Colorado Springs

Research output: Contribution to journal › Article › peer-review

128 Citations (SciVal)

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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 (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.

Original language	English
Pages (from-to)	3883-3895
Number of pages	13
Journal	Journal of Proteome Research
Volume	15
Issue number	10
Early online date	20 Sept 2016
DOIs	https://doi.org/10.1021/acs.jproteome.6b00733
Publication status	Published - 7 Oct 2016

Bibliographical note

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

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10.1021/acs.jproteome.6b00733

AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia
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
Accepted author manuscript, 2.71 MB

Cite this

d’Alessandro, A., Nemkov, T., Sun, K., Liu, H., Song, A., Monte, A. A., Subudhi, A. W., Lovering, A. T., Dvorkin, D., Julian, C. G., Kevil, C. G., Kolluru, G. K., Shiva, S., Gladwin, M. T., Xia, Y., Hansen, K. C., & Roach, R. C. (2016). AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia. Journal of Proteome Research, 15(10), 3883-3895. https://doi.org/10.1021/acs.jproteome.6b00733

@article{1b8f606acbff416bb1ee30bc363e4a99,

title = "AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia",

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 (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.",

author = "Angelo d{\textquoteright}Alessandro and Travis Nemkov and Kaiqi Sun and Hong Liu and Anren Song and Monte, \{Andrew A.\} and Subudhi, \{Andrew W.\} and Lovering, \{Andrew T.\} and Daniel Dvorkin and Julian, \{Colleen G.\} and Kevil, \{Christopher G.\} and Kolluru, \{Gopi K.\} and Sruti Shiva and Gladwin, \{Mark T.\} and Yang Xia and Hansen, \{Kirk C.\} and Roach, \{Robert C.\}",

note = "This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright {\textcopyright} 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 ",

year = "2016",

month = oct,

day = "7",

doi = "10.1021/acs.jproteome.6b00733",

language = "English",

volume = "15",

pages = "3883--3895",

journal = "Journal of Proteome Research",

issn = "1535-3893",

publisher = "American Chemical Society",

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d’Alessandro, A, Nemkov, T, Sun, K, Liu, H, Song, A, Monte, AA, Subudhi, AW, Lovering, AT, Dvorkin, D, Julian, CG, Kevil, CG, Kolluru, GK, Shiva, S, Gladwin, MT, Xia, Y, Hansen, KC & Roach, RC 2016, 'AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia', Journal of Proteome Research, vol. 15, no. 10, pp. 3883-3895. https://doi.org/10.1021/acs.jproteome.6b00733

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 -

AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia

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