title: Hypobaric hypoxia and reoxygenation induce proteomic profile changes in the rat brain cortex.
abstract: Brain, due to its high metabolism, is severely affected by hypoxia/reoxygenation. In this study, cerebral cortexes from rats subjected to hypobaric hypoxia followed by several reoxygenation periods (0 h, 24 h, and 5 days) were compared with normobaric normoxic controls to identify protein-expression differences using proteomic approaches. Only 2-fold differences in spot abundance between controls and experimental groups from each reoxygenation period were considered. The proteins identified were grouped into categories, according to their similarity in function or to their involvement in the same metabolic pathway. We distinguished five groups: (1) glycolysis, including γ-enolase (NSE), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH); (2) tricarboxylic acid cycle, such as aconitate hydratase (ACO2); (3) oxidative phosphorylation, like F1-ATPase chains α and β; (4) cytoskeletal, including Spna2, α-tubulin, β-tubulin, β-actin, and microtubule-associated protein RP/EB family member 3 (EB3); and (5) chaperones, like heat-shock protein 72 kDa (HSP72). NSE was upregulated while GAPDH was downregulated, both peaking at 5 days post-hypoxia. ACO2 and F1-ATPase decreased in all the reoxygenation periods. Spna2 and EB3 were expressed neither in control nor at 0 h, but 5 days post-hypoxia new expression took place. The α- and β-tubulin levels significantly fell at 0 h, but after 24 h strongly increased. Also, β-actin and HSP72 were downregulated, and the last one reached the lowest level at 24 h of reoxygenation. We conclude that the molecular mechanisms underlying hypoxia/reoxygenation in the rat cortex might consist of a close relationship between energy metabolism, cytoskeleton, and chaperones. These findings may shed light on therapeutic targets against hypoxia-related damage.
authors.affiliation: Area of Cellular Biology, Department of Experimental Biology (Building B-3), University of Jaén, Campus Las Lagunillas s/n, 23071, Jaén, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Hernández
authors.forename: Santos
authors.initials: S
authors.lastname: Blanco
authors.forename: Juan
authors.initials: J
authors.lastname: Peragón
authors.forename: Juan Á
authors.initials: JÁ
authors.lastname: Pedrosa
authors.forename: María Á
authors.initials: MÁ
authors.lastname: Peinado
mesh_terms: D000818:Animals; D001273:Atmosphere Exposure Chambers; D001274:Atmospheric Pressure; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000378:metabolism*; D002952:Citric Acid Cycle; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D006019:Glycolysis; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000494:pharmacology; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D010100:Oxygen