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AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

ABSTRACT: An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n?=?14) or 21 (n?=?7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

SUBMITTER: Subudhi AW

PROVIDER: S-EPMC3962396 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

Subudhi Andrew W AW Bourdillon Nicolas N Bucher Jenna J Davis Christopher C Elliott Jonathan E JE Eutermoster Morgan M Evero Oghenero O Fan Jui-Lin JL Jameson-Van Houten Sonja S Julian Colleen G CG Kark Jonathan J Kark Sherri S Kayser Bengt B Kern Julia P JP Kim See Eun SE Lathan Corinna C Laurie Steven S SS Lovering Andrew T AT Paterson Ryan R Polaner David M DM Ryan Benjamin J BJ Spira James L JL Tsao Jack W JW Wachsmuth Nadine B NB Roach Robert C RC

PloS one 20140321 3

An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these find ...[more]

PMID: 24658407

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Project description:ObjectiveHigh altitude hypobaric hypoxia can induce hearing impairment and hearing acclimatization, but few studies have been performed to decipher the potential transition between the two states. To decipher transition-related circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNA (mRNAs) regulatory network.MethodsWistar rats were airlifted from plain to high altitude and maintained for 30 days and 60 days. Hearing acclimatization was determined using the Auditory Brainstem Response (ABR) test. Cochlea tissues were isolated, and high-throughput circRNA analysis and mRNAs-sequencing were performed. Differentially Expressed circRNAs (DEcircRNAs) and Differentially Expressed mRNAs (DEmRNAs) were obtained, and circRNA-miRNA and miRNA-mRNA regulation were predicted. A circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was also constructed. The DEmRNAs in this network were functionally annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses based on Metascape.ResultsThe ABR assay indicated that hearing impairment happened on day 30 and hearing acclimatization occurred on day 60. Hearing impairment-related circRNAs (64 upregulated and 147 downregulated) and genes (572 upregulated and 757 downregulated) were identified. Hearing acclimatization-related circRNAs (79 upregulated and 142 downregulated) and genes (690 upregulated and 751 downregulated) were also identified. Hearing impairment and hearing acclimatization ceRNA networks were also constructed after integrating the predicted miRNA regulation analyses. Anterograde trans-synaptic signaling (GO:0098916) and negative regulation of cellular response to growth factor stimulus (GO:0090288) were regulated by hearing impairment ceRNA networks, and embryonic organ development (GO:0048568) was regulated by hearing acclimatization ceRNA networks.ConclusionHearing impairment- and hearing acclimatization-associated circRNAs and ceRNA networks were identified, which contribute new knowledge to our understanding of acclimatization transition.

Dataset Information

AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

Publications

AltitudeOmics: the integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent.

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