Decoding Proteomic cross-talk between hypobaric and normobaric hypoxia: Integrative analysis of oxidative stress, cytoskeleton remodeling, and inflammatory pathways

Abstract

Aims

To investigate the differential regulation of proteomic landscapes elicited by hypobaric hypoxia (HH) and normobaric hypoxia (NH) and to shed light on the molecular cross-talk underlying pre-acclimatization strategies.

Materials and methods

Label-free LCMS-MS quantitative proteomics was employed to evaluate the lung tissues of SD rats (n = 6) subjected to 6 h of acute HH at 25,000 ft associated with reduced barometric pressure, 282 mmHg, and NH at 8 % FiO2.

Key findings

Our findings indicate that NH facilitated the minimal downregulation of proteins involved in maintaining pulmonary cytoskeleton integrity, including calpain 2, vitronectin, and beta-arrestin 1, whereas HH leads to severe downregulation of these proteins, causing a greater cytoskeleton disruption. Proteins contributing to redox homeostasis such as iNOS and SOD, were upregulated in both hypoxic conditions. However, SIRT1-mediated ROS-triggered proteins, including FOXO1 and FOXO4, exhibited upregulation in HH and downregulation in NH. Other proteins, HIF-1α and IDH, were upregulated in HH compared to NH. Additionally, Hemopexin was severely downregulated in HH relative to NH.

Significance

For the first time, this study uncovers the comparative proteomic analysis of two distinct pre-acclimatization interventions by employing varied hypoxia modeling strategies highlighting the key molecular mechanism involved in HH acclimatization induced by differential hypoxia simulating technique.