title: Delayed bradykinin postconditioning modulates intrinsic neuroprotective enzyme expression in the rat CA1 region after cerebral ischemia: a proteomic study.
abstract: Pyramidal cells in the CA1 brain region exhibit an ischemic tolerance after delayed postconditioning; therefore, this approach seems to be a promising neuroprotective procedure in cerebral postischemic injury improvement. However, little is known about the effect of postconditioning on protein expression patterns in the brain, especially in the affected hippocampal neurons after global cerebral ischemia. This study is focused on the examination of the ischemia-vulnerable CA1 neuronal layer and on the acquisition of protection from delayed neuronal death after ischemia. Ischemic-reperfusion injury was induced in Wistar rats and bradykinin was applied 2 days after the ischemic insult in an attempt to overcome delayed cell death. Analysis of complex peptide CA1 samples was performed by automated two dimensional liquid chromatography (2D-LC) fractionation coupled to tandem matrix assisted laser desorption/ionization time-of-flight (MALDI TOF/TOF) mass spectrometry instrumentation. We devoted our attention to differences in protein expression mapping in ischemic injured CA1 neurons in comparison with equally affected neurons, but with bradykinin application. Proteomic analysis identified several proteins occurring only after postconditioning and control, which could have a potentially neuroprotective influence on ischemic injured neurons. Among them, the prominent position occupies a regulator of glutamate level aspartate transaminase AATC, a scavenger of glutamate in brain neuroprotection after ischemia-reperfusion. We identified this enzyme in controls and after postconditioning, but AATC presence was not detected in the ischemic injured CA1 region. This finding was confirmed by two-dimensional differential electrophoresis followed by MALDI-TOF/TOF MS identification. Results suggest that bradykinin as delayed postconditioning may be associated with modulation of protein expression after ischemic injury and thus this procedure can be involved in neuroprotective metabolic pathways.
authors.affiliation: Institute of Neurobiology, SAS, Kosice, Slovakia. nemeth@saske.sk.
authors.forename: Miroslava
authors.identifier: 0000-0002-2841-8009
authors.initials: M
authors.lastname: Nemethova
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, P. J. Safarik University, Kosice, Slovakia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Talian
authors.affiliation: Institute of Neurobiology, SAS, Kosice, Slovakia.
authors.forename: Viera
authors.initials: V
authors.lastname: Danielisova
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, P. J. Safarik University, Kosice, Slovakia.
authors.forename: Sona
authors.initials: S
authors.lastname: Tkacikova
authors.affiliation: Institute of Neurobiology, SAS, Kosice, Slovakia.
authors.forename: Petra
authors.initials: P
authors.lastname: Bonova
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, P. J. Safarik University, Kosice, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Bober
authors.affiliation: Institute of Neurobiology, SAS, Kosice, Slovakia.
authors.forename: Milina
authors.initials: M
authors.lastname: Matiasova
authors.affiliation: Department of Medical and Clinical Biophysics, Faculty of Medicine, P. J. Safarik University, Kosice, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Sabo
authors.affiliation: Institute of Neurobiology, SAS, Kosice, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Burda
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage*; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D056547:CA1 Region, Hippocampal / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D040901:Proteomics / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors
chemical_list: D001920:Bradykinin
keywords: Cerebral ischemia; Hippocampus; MALDI; Postconditioning; Proteomics; Rat