title: Exploratory proteomic analysis of hypobaric hypoxia and acute mountain sickness in humans.
abstract: Our objective in this exploratory study was to identify novel biomarkers of importance for acute mountain sickness (AMS) using discovery-based proteomic methods. Peripheral blood samples were collected and AMS symptoms were assessed in 20 healthy volunteers prior to [-15 h (baseline) and 0 h; 1,609 m; barometric pressure = 625 mmHg] and after a 9-h exposure to hypobaric hypoxia (9 h; 4,875 m; barometric pressure = 425 mmHg). AMS status was assessed using the Lake Louise Questionnaire. Plasma samples were pooled according to AMS status at each time point. Protein composition of the samples was determined by a GeLC-MS/MS approach using two analytical platforms (LTQ-XL linear ion trap mass spectrometer and a LTQ-FT ultra hybrid mass spectrometer) for technical replication. Spectral counting was used to make semiquantitative comparisons of protein abundance between AMS-susceptible (AMS) and AMS-resistant (AMS·R) subjects with exposure to hypobaric hypoxia. After 9 h of hypoxia, the abundance of proteins with antioxidant properties (i.e., peroxiredoxin 6, glutathione peroxidase, and sulfhydryl oxidase 1) rose in AMS but not AMS·R. Our exploratory analyses suggest that exposure to hypobaric hypoxia enhances enzymatic antioxidant systems in AMS vs. AMS·R, which, we propose, may be an overcompensation for hypoxia-induced oxidant production. On the basis of our findings we 1) speculate that quenching oxidant activity may have adverse downstream effects that are of pathophysiological importance for AMS such as interrupting oxidant-sensitive cell signaling and gene transcription and 2) question the existing assumption that increased oxidant production in AMS is pathological.
authors.affiliation: Altitude Research Center, Department of Emergency Medicine, University of Colorado Denver, Aurora, Colorado;
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Julian
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Subudhi
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Hill
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Wilson
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dimmen
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Roach
mesh_terms: D000064:Acclimatization; D000208:Acute Disease; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood* / Q000175:diagnosis; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004798:Enzymes / Q000097:blood; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000175:diagnosis; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D001798:Blood Proteins; D004798:Enzymes
keywords: acute mountain sickness; hypoxia; proteomics