Comparative proteome analysis reveals differential regulation of glycolytic and antioxidant enzymes in cortex and hippocampus exposed to short-term hypobaric hypoxia.

Hypoxia is one of the major stressors at high altitude. Exposure to hypobaric hypoxia induces several adverse consequences to the structural and functional integrity of brain. In an attempt to understand the proteome modulation, we used 2-DE coupled with MALDI-TOF/TOF for cortex and hippocampus exposed to short-term temporal (0, 3, 6, 12 and 24h) hypobaric hypoxia. This enabled us in the identification of 88 and 73 hypoxia responsive proteins in cortex and hippocampus respectively. We further compared the proteomes of both the regions and identified 37 common proteins along with 49 and 32 specific proteins for cortex and hippocampus respectively. We observed significant up-regulation of glycolytic enzymes like Gapdh, Pgam1, Eno1 and malate-aspartate shuttle enzymes Mdh1 and Got1in cortex as compared to hippocampus deciphering efficient use of energy producing substrates. This was coupled with concomitant increase in expression of antioxidant enzymes like Sod1, Sod2 and Pebp1 in cortex to neutralize the hypoxia-induced reactive oxygen species (ROS) generation. Our comparative proteomics studies demonstrate that efficient use of energy generating pathways in conjugation with abundance of antioxidant enzymes makes cortex less vulnerable to hypoxia than hippocampus.