title: HIF1α and physiological responses to hypoxia are correlated in mice but not in rats.
abstract: We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), display divergent physiological responses to high altitude, including improved respiratory and metabolic control in mice. In the present study, we asked whether these traits would also be present in response to hypoxia at sea level. To answer this question, we exposed rats (Sprague Dawley) and mice (FVB) to normoxia (21% O2) or hypoxia (15 and 12% O2) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1α (ELISA and mass spectrometry) and other proteins whose expression are regulated by hypoxia (glucose transporter 1, pyruvate dehydrogenase kinase 1 and angiopoietin 2; mass spectrometry) in the brainstem. In response to hypoxia, compared with rats, mice had higher minute ventilation, lower metabolic rate and higher expression of HIF-1α in the brainstem. In mice, the expression level of HIF-1α was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O2, while expression of the glucose transporter 1 increased. We conclude that mice and rats raised at sea level have divergent physiological and molecular responses to hypoxia, supporting the hypothesis that mice have innate traits that favor adaptation to altitude.
authors.affiliation: Unité de recherche en périnatologie, Centre Hospitalier Universitaire de Québec, Hôpital Saint-François d'Assise, Département de Pédiatrie, Université Laval, Québec, QC, Canada G1L 3L5.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jochmans-Lemoine
authors.affiliation: Unité de recherche en périnatologie, Centre Hospitalier Universitaire de Québec, Hôpital Saint-François d'Assise, Département de Pédiatrie, Université Laval, Québec, QC, Canada G1L 3L5.
authors.forename: Manju
authors.initials: M
authors.lastname: Shahare
authors.affiliation: Unité de recherche en périnatologie, Centre Hospitalier Universitaire de Québec, Hôpital Saint-François d'Assise, Département de Pédiatrie, Université Laval, Québec, QC, Canada G1L 3L5.
authors.forename: Jorge
authors.initials: J
authors.lastname: Soliz
authors.affiliation: Unité de recherche en périnatologie, Centre Hospitalier Universitaire de Québec, Hôpital Saint-François d'Assise, Département de Pédiatrie, Université Laval, Québec, QC, Canada G1L 3L5 vincentjoseph@fmed.ulaval.ca.
authors.forename: Vincent
authors.identifier: 0000-0003-3571-9042
authors.initials: V
authors.lastname: Joseph
mesh_terms: D000531:Altitude; D000818:Animals; D001481:Basal Metabolism; D001838:Bolivia; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005843:Geography; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D051379:Mice; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013347:Subcellular Fractions / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; C497443:Hif1a protein, mouse; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035181:TATA-Box Binding Protein
keywords: Brain; Hypoxia; Metabolic rate; Protein expression; Respiratory control