Changes in excitatory amino acid transporters in response to remote ischaemic preconditioning and glutamate excitotoxicity.

Autor: Končeková J; Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, Soltesovej 4-6, Košice, 040 01, Slovak Republic., Kotorová K; Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, Soltesovej 4-6, Košice, 040 01, Slovak Republic., Gottlieb M; Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, Soltesovej 4-6, Košice, 040 01, Slovak Republic., Bona M; Department of Medical Physiology, Faculty of Medicine, University of Pavol Jozef Safarik, Košice, 040 01, Slovak Republic., Bonová P; Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, Soltesovej 4-6, Košice, 040 01, Slovak Republic. Electronic address: bonova@saske.sk.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2024 Feb; Vol. 173, pp. 105658. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1016/j.neuint.2023.105658
Abstrakt: The successful implementation of remote ischaemic conditioning as a clinical neuroprotective strategy requires a thorough understanding of its basic principles, which can be modified for each patient. The mechanisms of glutamate homeostasis appear to be a key component. In the current study, we focused on the brain-to-blood glutamate shift mediated by glutamate transporters (excitatory amino acid transports [EAATs]) and the effect of remote ischaemic preconditioning (RIPC) as a mediator of ischaemic tolerance. We used model mimicking ischaemia-mediated excitotoxicity (intracerebroventricular administration of glutamate) to avoid the indirect effect of ischaemia-triggered mechanisms. We found quantitative changes in EAAT2 and EAAT3 and altered membrane trafficking of EAAT1 on the cells of the choroid plexus. These changes could underlie the beneficial effects of ischaemic tolerance. There was reduced oxidative stress and increased glutathione level after RIPC treatment. Moreover, we determined the stimulus-specific response on EAATs. While glutamate overdose stimulated EAAT2 and EAAT3 overexpression, RIPC induced membrane trafficking of EAAT1 and EAAT2 rather than a change in their expression. Taken together, mechanisms related to glutamate homeostasis, especially EAAT-mediated transport, represents a powerful tool of ischaemic tolerance and allow a certain amount of flexibility based on the stimulus used.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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