The proteome of Hypobaric Induced Hypoxic Lung: Insights from Temporal Proteomic Profiling for Biomarker Discovery

Abstract

Exposure to high altitude induces physiological responses due to hypoxia. Lungs being at the first level to face the alterations in oxygen levels are critical to counter and balance these changes. Studies have been done analysing pulmonary proteome alterations in response to exposure to hypobaric hypoxia. However, such studies have reported the alterations at specific time points and do not reflect the gradual proteomic changes. These studies also identify the various biochemical pathways and responses induced after immediate exposure and the resolution of these effects in challenge to hypobaric hypoxia. In the present study, using 2-DE/MS approach, we attempt to resolve these shortcomings by analysing the proteome alterations in lungs in response to different durations of exposure to hypobaric hypoxia. Our study thus highlights the gradual and dynamic changes in pulmonary proteome following hypobaric hypoxia. For the first time, we also report the possible consideration of SULT1A1, as a biomarker for the diagnosis of high altitude pulmonary edema (HAPE). Higher SULT1A1 levels were observed in rats as well as in humans exposed to high altitude, when compared to sea-level controls. This study can thus form the basis for identifying biomarkers for diagnostic and prognostic purposes in responses to hypobaric hypoxia.

Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer

“…Gene Ontology annotations including cellular component, biological process, and molecular function were performed with Blast2GO program (Version 2.7.0) [30–32]. A global protein-protein interaction network was generated using Cytoscape (Version 3.1) [33, 34].…”

Revisiting cobalt chloride preconditioning to prevent hypobaric hypoxia-induced damage: identification of global proteomic alteration and key networks

“…After electrophoresis, proteins were visualized by modified silver staining procedure compatible with MS (Villanueva et al 2004) previously described by Ahmad et al (Ahmad and Sharma 2009;Ahmad et al 2014Ahmad et al , 2015. Briefly, the gels were fixed in a fixing solution (50 % v/v methanol, 12 % v/v acetic acid and 0.05 % v/v formaldehyde).…”

“…Briefly, the 500 ug of precipitated plasma protein from each sample was separated in first dimension using I m m o b i l i n e D r y S t r i p s ( 1 7 c m , p H 4 -7 , G E Healthcare, Sweden) strictly, as per the condition described previously by Ahmad et al (Ahmad and Sharma 2009;Ahmad et al 2014Ahmad et al , 2015, followed by second dimension separation on polyacrylamide gels.…”

Deciphering Molecular Cascades in a Novel Acclimatization Strategy for Rapid Ascent to High Altitude

“…We have checked the effects of acute (24 h) exposure to simulated altitudes of 10,000 ft (high altitude zone), 15,000 ft (very high altitude zone) and 25,000 ft (extreme altitude zone) on SD rats at the proteome and oxidative stress specific transcripts levels. Our previous work stating the feasibility and statistical robustness of Sult1A1 as a marker for hypobaric hypoxia stress (and HAPE) and 24 h being the unique time-point showing maximal perturbations within the proteome[23] are also being re-invoked here in the context of altitude variation. Consequently, based on molecular cascades, can there be preventive diagnosis for establishing objectively if an individual is acclimatizing or not based on molecular events much before life-threatening physiological consequences of hypobaric hypoxia occur.…”