Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure.
Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies.
1 Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences , Defence Research and Development Organization, Timarpur, Delhi, India .
Gayatri
G
Padhy
Niroj Kumar
NK
Sethy
Lilly
L
Ganju
Kalpana
K
Bhargava
D000531:Altitude; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000097:blood; D043303:Aryldialkylphosphatase / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000097:blood*; D006242:Haptoglobins / Q000378:metabolism; D006985:Hyperventilation / Q000097:blood / Q000209:etiology; D000860:Hypoxia / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D037181:Lectins, C-Type / Q000097:blood; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011228:Prealbumin / Q000378:metabolism*; D011312:Pressure; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation; D020692:rab3 GTP-Binding Proteins / Q000097:blood
D000975:Antioxidants; D016632:Apolipoprotein A-I; D003176:Complement C3; D003181:Complement C4; D006242:Haptoglobins; D037181:Lectins, C-Type; D009566:Nitrates; D009573:Nitrites; D011228:Prealbumin; D002097:C-Reactive Protein; C505355:GPX3 protein, rat; D005979:Glutathione Peroxidase; C572204:Pon1 protein, rat; D043303:Aryldialkylphosphatase; C492133:Rab3d protein, rat; D020692:rab3 GTP-Binding Proteins