Activated corticosterone synthetic pathway is involved in poor responses to re-oxygenation after prolonged hypoxia

Chang Liu; Jian Chen; Bao Liu; Wen-Ting Liao; Jie Liu; Gang Xu; Bing-Da Sun; Er-Long Zhang; Yu-Qi Gao

Activated corticosterone synthetic pathway is involved in poor responses to re-oxygenation after prolonged hypoxia

Int J Clin Exp Pathol. 2017 Aug 1;10(8):8414-8423. eCollection 2017.

Authors

Chang Liu^{1

2

3}, Jian Chen^{1

2

3}, Bao Liu^{1

2

3}, Wen-Ting Liao^{1

2

3}, Jie Liu^{1

2

3}, Gang Xu^{1

2

3}, Bing-Da Sun^{1

2

3}, Er-Long Zhang^{1

2

3}, Yu-Qi Gao^{1

2

3}

Affiliations

¹ Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University Chongqing, China.
² Key Laboratory of High Altitude Environmental Medicine, Third Military Medical University, Ministry of Education Chongqing, China.
³ Key Laboratory of High Altitude Medicine, PLA Chongqing, China.

PMID: 31966693
PMCID: PMC6965453

Abstract

Diverse response patterns to re-oxygenation lead to various physiological or pathological phenotypes, but now lack of systematic research models in vivo. High-altitude de-acclimatization syndrome (HADAS) describes systematic alterations of re-oxygenation returning to plain after a long living in high altitude. In this study, we aim at employing a comprehensive metabolomics to explore the mechanisms for different reactions to re-oxygenation based on systematic quantitation scoring methods of HADAS model. Plasma samples were collected from 22 subjects when they finished their stay in high altitude for 1 year (5300 m), returning plain for 30^th day and 180^th day. These participants were divided into HADAS-S or HADAS-R group based on HADAS model on the 30^th day after their reaching. Metabolic profiling was performed by ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analysis. A total of 20 differential metabolites were identified by the comparison between HADAS-S and HADAS-R group. Pathway analysis suggested that the most potential disturbed pathway is sterol synthesis pathway, especially corticosterone synthetic sub-pathway. These molecules detected in this pathway are detailed that they showed a rapid and significant increasing manner in HADAS-S subjects comparing to HADAS-R group in the process of re-oxygenation. In conclusion, we identified that excessive stress responses to re-oxygenation might contribute to the distinctions between HADAS-S and HADAS-R group. These findings provide novel insights for further understanding of the pathogenesis for metabolic abnormalities in re-oxygenation after prolonged hypoxia.

Keywords: Re-oxygenation; UPLC-QTOF/MS; human plasma; hypoxia; metabolic profiling.