Proteomic identification of novel differentiation plasma protein markers in hypobaric hypoxia-induced rat model.
BACKGROUND
Hypobaric hypoxia causes complex changes in the expression of genes, including stress related genes and corresponding proteins that are necessary to maintain homeostasis. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of complex and dynamic changes that occur during the hypobaric hypoxia.


METHODS
In this study we investigated the temporal plasma protein alterations of rat induced by hypobaric hypoxia at a simulated altitude of 7620 m (25,000 ft, 282 mm Hg) in a hypobaric chamber. Total plasma proteins collected at different time points (0, 6, 12 and 24 h), separated by two-dimensional electrophoresis (2-DE) and identified using matrix assisted laser desorption ionization time of flight (MALDI-TOF/TOF). Biological processes that were enriched in the plasma proteins during hypobaric hypoxia were identified using Gene Ontology (GO) analysis. According to their properties and obvious alterations during hypobaric hypoxia, changes of plasma concentrations of Ttr, Prdx-2, Gpx -3, Apo A-I, Hp, Apo-E, Fetub and Nme were selected to be validated by Western blot analysis.


RESULTS
Bioinformatics analysis of 25 differentially expressed proteins showed that 23 had corresponding candidates in the database. The expression patterns of the eight selected proteins observed by Western blot were in agreement with 2-DE results, thus confirming the reliability of the proteomic analysis. Most of the proteins identified are related to cellular defense mechanisms involving anti-inflammatory and antioxidant activity. Their presence reflects the consequence of serial cascades initiated by hypobaric hypoxia.


CONCLUSIONS
This study provides information about the plasma proteome changes induced in response to hypobaric hypoxia and thus identification of the candidate proteins which can act as novel biomarkers.
Peptide and Proteomics Division, DIPAS, DRDO, Ministry of Defence, Delhi, India.
Yasmin
Y
Ahmad
Peptide and Proteomics Division, DIPAS, DRDO, Ministry of Defence, Delhi, India.
Narendra K
NK
Sharma
Department of Chemistry, Jamia Millia Islamia, New Delhi, India.
Mohammad Faiz
MF
Ahmad
Peptide and Proteomics Division, DIPAS, DRDO, Ministry of Defence, Delhi, India.
Manish
M
Sharma
Department of Genomics, DIPAS, DRDO, Ministry of Defence, Delhi, India.
Iti
I
Garg
Peptide and Proteomics Division, DIPAS, DRDO, Ministry of Defence, Delhi, India.
Kalpana
K
Bhargava
D000399:Air Pressure; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D063990:Gene Ontology; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D015415:Biomarkers; D001798:Blood Proteins