An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

Yasmin Ahmad,Mohammad Faiz Ahmad,Manish Sharma,Kalpana Bhargava,Narendra K Sharma,Iti Garg,Rizwan H Khan

doi:10.1371/journal.pone.0067548

Abstract

Adaptation to hypobaric hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importance to shed light on the mechanisms known to counteract the negative effects of oxygen lack. To obtain a molecular signature, changes in the plasma proteome were studied by using proteomic approach. To enrich the low-abundance proteins in human plasma, two highly abundant proteins, albumin and IgG, were first removed. By comparing the plasma proteins of high altitude natives with those of a normal control group, several proteins with a significant alteration were found. The up-regulated proteins were identified as vitamin D-binding protein, hemopexin, alpha-1–antitrypsin, haptoglobin β-chain, apolipoprotein A1, transthyretin and hemoglobin beta chain. The down-regulated proteins were transferrin, complement C3, serum amyloid, complement component 4A and plasma retinol binding protein. Among these proteins, the alterations of transthyretin and transferrin were further confirmed by ELISA and Western blotting analysis. Since all the up- and down- regulated proteins identified above are well-known inflammation inhibitors and play a positive anti-inflammatory role, these results show that there is some adaptive mechanism that sustains the inflammation balance in high altitude natives exposed to hypobaric hypoxia.

Highlights

The stress at high altitude is hypobaric hypoxia resulting from the lowered barometric pressure
Hypoxia response elements containing HIF-1 binding sites were identified in genes encoding transferrin [6], vascular endothelium growth factor (VEGF) [7,8], inducible nitric oxide synthase [9], glucose transporter 1 (GLUT 1) [10], and several glycolytic enzymes, all playing important roles in systemic, tissues, or intracellular O2 homeostasis allowing for increased anaerobic ATP synthesis
The results showed that most of the plasma proteins found in high altitude natives are acute phase proteins (APPs), compliment components and apolipoproteins and so on

Summary

Introduction

The stress at high altitude is hypobaric hypoxia resulting from the lowered barometric pressure. It is unavoidable, un-modifiable, and uniform for everyone at any given altitude. HIF was identified originally by its binding to a hypoxia response element in the human erythropoietin gene [4,5]. Hypoxia response elements containing HIF-1 binding sites were identified in genes encoding transferrin [6], vascular endothelium growth factor (VEGF) [7,8], inducible nitric oxide synthase (iNOS) [9], glucose transporter 1 (GLUT 1) [10], and several glycolytic enzymes, all playing important roles in systemic, tissues, or intracellular O2 homeostasis allowing for increased anaerobic ATP synthesis. Some molecular variables involved in the defense against hypobaric hypoxia were identified in animal models and at cellular level [10,11]

Methods

Results

Conclusion