Abstract

Although extensive studies have focused on the development of acute mountain sickness (AMS), the exact mechanisms of AMS are still obscure. In this study, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis to identify novel AMS−associated biomarkers in human plasma. After 9 hours of hypobaric hypoxia the abundance of proteins related to tricarboxylic acid (TCA) cycle, glycolysis, ribosome, and proteasome were significantly reduced in AMS resistant (AMS−) group, but not in AMS susceptible (AMS+) group. This suggested that AMS− individuals could reduce oxygen consumption via repressing TCA cycle and glycolysis, and reduce energy consumption through decreasing protein degradation and synthesis compared to AMS+ individuals after acute hypoxic exposure. The inflammatory response might be decreased resulting from the repressed TCA cycle. We propose that the ability for oxygen consumption reduction may play an important role in the development of AMS. Our present plasma proteomic study in plateau of the Han Chinese volunteers gives new data to address the development of AMS and potential AMS correlative biomarkers.

Highlights

  • Acute mountain sickness (AMS) is a transient medical condition characterized by headache, nausea, fatigue, dizziness and insomnia that usually occur within 6–12 h after rapid ascent to high altitudes above 2500 m in non-altitude acclimatized individuals[1]

  • To determine the most prominent functional protein groups that differed in response to hypobaric hypoxia in acute mountain sickness (AMS)− subjects, we performed Gene Ontology (GO) analysis and identified that the affected proteins enriched in the metabolic process, cellular process, organic substance metabolic process, single-organism process and so on

  • To reveal the most prominent functional protein groups that differed in response to hypobaric hypoxia in AMS− individuals, GO biological process analysis was performed, and we found that the affected proteins were involved in cellular process, metabolic process, organic substance metabolic process, and primary metabolic process and so on

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Summary

Introduction

Acute mountain sickness (AMS) is a transient medical condition characterized by headache, nausea, fatigue, dizziness and insomnia that usually occur within 6–12 h after rapid ascent to high altitudes above 2500 m in non-altitude acclimatized individuals[1]. Genetic and proteomic studies showed that certain biomarkers might be involved in AMS development. The levels of these biomarkers are different in AMS susceptible (AMS+) individuals and AMS resistant (AMS−) individuals[5,8]. It is helpful to explore the AMS−associated biomarkers for addressing the mechanism of AMS. Proteomics method can be used to analyze plasma samples from AMS− and AMS+ individuals to find the AMS−associated biomarkers. We compared the changes in proteome of plasma samples between AMS+ group and AMS− group after an acute exposure to high altitudes. Our study suggested that AMS− individuals might be more capable to down-regulate oxygen consumption than AMS+ individuals after acute hypobaric hypoxic exposure

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