Interplay of lung cytoskeletal re-modeling, energy metabolism and
inflammation during extended exposures to lowered pO2
Abstract
Extended exposure to low pO2 has multiple effects on signaling cascades.
Despite multiple exploratory studies, specific studies elucidating the
response of lung and plasma proteome in context of surviving low pO2
exposures are lacking. In this study, we simulated low pO2(PB=40 kPa;
7620 m) exposure in male Sprague-Dawley (SD) rats for 3, 7 and 14 days.
Redox stress assays and proteomics were performed using lung and plasma
followed by protein network analyses. We observed that redox homeostasis
was achieved after day 3 of exposure. Lung proteome revealed
cytoskeletal processes were the most significant with STAT3 acting as
upstream regulator. Plasma proteome revealed a focus on lipid metabolism
derived inflammatory processes. Overall, during prolonged low pO2
exposure, particularly those involving slowly decreasing pressures,
redox homeostasis is achieved but energy metabolism is perturbed and
this leads to an immune/inflammatory signaling impetus after 3rd day of
exposure. We found that an interplay of lung cytoskeletal elements,
systemic energy metabolism and inflammatory proteins aid in achieving
redox homeostasis and surviving extended low pO2 exposures. Qualitative
perturbations to cytoskeletal stability and innate immunity/inflammation
were also observed during extended low pO2 exposure in humans exposed to
14,000 ft for 7, 14 and 21 days.