Molecular Bases of Brain Preconditioning
Preconditioning of the brain induces tolerance to the damaging effects of ischemia and prevents cell death in ischemic penumbra. The development of this phenomenon is mediated by mitochondrial adenosine triphosphate-sensitive potassium (KATP+) channels and nitric oxide signaling (NO). The aim of thi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2017.00427/full |
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| author | Oleg G. Deryagin Svetlana A. Gavrilova Khalil L. Gainutdinov Khalil L. Gainutdinov Anna V. Golubeva Vyatcheslav V. Andrianov Vyatcheslav V. Andrianov Guzel G. Yafarova Guzel G. Yafarova Sergey V. Buravkov Vladimir B. Koshelev |
| author_facet | Oleg G. Deryagin Svetlana A. Gavrilova Khalil L. Gainutdinov Khalil L. Gainutdinov Anna V. Golubeva Vyatcheslav V. Andrianov Vyatcheslav V. Andrianov Guzel G. Yafarova Guzel G. Yafarova Sergey V. Buravkov Vladimir B. Koshelev |
| author_sort | Oleg G. Deryagin |
| collection | DOAJ |
| description | Preconditioning of the brain induces tolerance to the damaging effects of ischemia and prevents cell death in ischemic penumbra. The development of this phenomenon is mediated by mitochondrial adenosine triphosphate-sensitive potassium (KATP+) channels and nitric oxide signaling (NO). The aim of this study was to investigate the dynamics of molecular changes in mitochondria after ischemic preconditioning (IP) and the effect of pharmacological preconditioning (PhP) with the KATP+-channels opener diazoxide on NO levels after ischemic stroke in rats. Immunofluorescence-histochemistry and laser-confocal microscopy were applied to evaluate the cortical expression of electron transport chain enzymes, mitochondrial KATP+-channels, neuronal and inducible NO-synthases, as well as the dynamics of nitrosylation and nitration of proteins in rats during the early and delayed phases of IP. NO cerebral content was studied with electron paramagnetic resonance (EPR) spectroscopy using spin trapping. We found that 24 h after IP in rats, there is a two-fold decrease in expression of mitochondrial KATP+-channels (p = 0.012) in nervous tissue, a comparable increase in expression of cytochrome c oxidase (p = 0.008), and a decrease in intensity of protein S-nitrosylation and nitration (p = 0.0004 and p = 0.001, respectively). PhP led to a 56% reduction of free NO concentration 72 h after ischemic stroke simulation (p = 0.002). We attribute this result to the restructuring of tissue energy metabolism, namely the provision of increased catalytic sites to mitochondria and the increased elimination of NO, which prevents a decrease in cell sensitivity to oxygen during subsequent periods of severe ischemia. |
| first_indexed | 2024-12-20T17:51:15Z |
| format | Article |
| id | doaj.art-fb4da50b2c424b5a9642dcadea348ecd |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-20T17:51:15Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-fb4da50b2c424b5a9642dcadea348ecd2022-12-21T19:30:51ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-07-011110.3389/fnins.2017.00427274900Molecular Bases of Brain PreconditioningOleg G. Deryagin0Svetlana A. Gavrilova1Khalil L. Gainutdinov2Khalil L. Gainutdinov3Anna V. Golubeva4Vyatcheslav V. Andrianov5Vyatcheslav V. Andrianov6Guzel G. Yafarova7Guzel G. Yafarova8Sergey V. Buravkov9Vladimir B. Koshelev10Department of Physiology and General Pathology, Medical Faculty, Lomonosov Moscow State UniversityMoscow, RussiaDepartment of Physiology and General Pathology, Medical Faculty, Lomonosov Moscow State UniversityMoscow, RussiaLaboratory of Neurorehabilitation of Motor Disorders, Institute of Fundamental Medicine and Biology, Kazan Federal UniversityKazan, RussiaLaboratory of Spin Physics and Spin Chemistry, Zavoisky Physical-Technical Institute of the Russian Academy of SciencesKazan, RussiaDepartment of Physiology and General Pathology, Medical Faculty, Lomonosov Moscow State UniversityMoscow, RussiaLaboratory of Neurorehabilitation of Motor Disorders, Institute of Fundamental Medicine and Biology, Kazan Federal UniversityKazan, RussiaLaboratory of Spin Physics and Spin Chemistry, Zavoisky Physical-Technical Institute of the Russian Academy of SciencesKazan, RussiaLaboratory of Neurorehabilitation of Motor Disorders, Institute of Fundamental Medicine and Biology, Kazan Federal UniversityKazan, RussiaLaboratory of Spin Physics and Spin Chemistry, Zavoisky Physical-Technical Institute of the Russian Academy of SciencesKazan, RussiaResearch Laboratory of Cellular Structure and Tissue Imaging Analysis, Medical Faculty, Lomonosov Moscow State UniversityMoscow, RussiaDepartment of Physiology and General Pathology, Medical Faculty, Lomonosov Moscow State UniversityMoscow, RussiaPreconditioning of the brain induces tolerance to the damaging effects of ischemia and prevents cell death in ischemic penumbra. The development of this phenomenon is mediated by mitochondrial adenosine triphosphate-sensitive potassium (KATP+) channels and nitric oxide signaling (NO). The aim of this study was to investigate the dynamics of molecular changes in mitochondria after ischemic preconditioning (IP) and the effect of pharmacological preconditioning (PhP) with the KATP+-channels opener diazoxide on NO levels after ischemic stroke in rats. Immunofluorescence-histochemistry and laser-confocal microscopy were applied to evaluate the cortical expression of electron transport chain enzymes, mitochondrial KATP+-channels, neuronal and inducible NO-synthases, as well as the dynamics of nitrosylation and nitration of proteins in rats during the early and delayed phases of IP. NO cerebral content was studied with electron paramagnetic resonance (EPR) spectroscopy using spin trapping. We found that 24 h after IP in rats, there is a two-fold decrease in expression of mitochondrial KATP+-channels (p = 0.012) in nervous tissue, a comparable increase in expression of cytochrome c oxidase (p = 0.008), and a decrease in intensity of protein S-nitrosylation and nitration (p = 0.0004 and p = 0.001, respectively). PhP led to a 56% reduction of free NO concentration 72 h after ischemic stroke simulation (p = 0.002). We attribute this result to the restructuring of tissue energy metabolism, namely the provision of increased catalytic sites to mitochondria and the increased elimination of NO, which prevents a decrease in cell sensitivity to oxygen during subsequent periods of severe ischemia.http://journal.frontiersin.org/article/10.3389/fnins.2017.00427/fullischemic preconditioningATP-sensitive potassium channelsnitric oxidemitochondrianeuroprotection |
| spellingShingle | Oleg G. Deryagin Svetlana A. Gavrilova Khalil L. Gainutdinov Khalil L. Gainutdinov Anna V. Golubeva Vyatcheslav V. Andrianov Vyatcheslav V. Andrianov Guzel G. Yafarova Guzel G. Yafarova Sergey V. Buravkov Vladimir B. Koshelev Molecular Bases of Brain Preconditioning Frontiers in Neuroscience ischemic preconditioning ATP-sensitive potassium channels nitric oxide mitochondria neuroprotection |
| title | Molecular Bases of Brain Preconditioning |
| title_full | Molecular Bases of Brain Preconditioning |
| title_fullStr | Molecular Bases of Brain Preconditioning |
| title_full_unstemmed | Molecular Bases of Brain Preconditioning |
| title_short | Molecular Bases of Brain Preconditioning |
| title_sort | molecular bases of brain preconditioning |
| topic | ischemic preconditioning ATP-sensitive potassium channels nitric oxide mitochondria neuroprotection |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2017.00427/full |
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