期刊
JOURNAL OF EXPERIMENTAL BIOLOGY
卷 219, 期 24, 页码 3952-3961出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jeb.142869
关键词
Respiratory control; Metabolic rate; Hypoxia; Protein expression; Brain
类别
资金
- Natural Sciences and Engineering Research Council of Canada [RGPGP-2014-00083]
- Reseau en Sante Respiratoire (Fonds de Recherche du Quebec - Sante)
- Reseau en Sante Respiratoire (Canadian Institutes of Health Research)
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% O-2) or hypoxia (15 and 12% O-2) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1 alpha (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-1 alpha in the brainstem. In mice, the expression level of HIF-1 alpha was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O-2, 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.
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