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The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsyстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Zavileyskiy Lev G., Aleshin Vasily A., Kaehne Thilo, Karlina Irina S., Artiukhov Artem V., Maslova Maria V., Graf Anastasia V., Bunik Victoria I.
- Журнал: International Journal of Molecular Sciences
- Том: 23
- Номер: 20
- Год издания: 2022
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 1
- Последняя страница: 17
- Номер статьи: 12302
- DOI: 10.3390/ijms232012302
- Аннотация: Abnormal energy expenditure during seizures and metabolic regulation through post-translational protein acylation suggest acylation as a therapeutic target in epilepsy. Our goal is to characterize an interplay between the brain acylation system components and their changes after seizures. In a rat model of pentylenetetrazole (PTZ)-induced epilepsy, we quantify 43 acylations in 29 cerebral cortex proteins; levels of NAD+; expression of NAD+-dependent deacylases (SIRT2, SIRT3, SIRT5); activities of the acyl-CoA-producing/NAD+-utilizing complexes of 2-oxoacid dehydrogenases. Compared to the control group, acylations of 14 sites in 11 proteins are found to differ significantly after seizures, with six of the proteins involved in glycolysis and energy metabolism. Comparing the single and chronic seizures does not reveal significant differences in the acylations, pyruvate dehydrogenase activity, SIRT2 expression or NAD+. On the contrary, expression of SIRT3, SIRT5 and activity of 2-oxoglutarate dehydrogenase (OGDH) decrease in chronic seizures vs a single seizure. Negative correlations between the protein succinylation/glutarylation and SIRT5 expression, and positive correlations between the protein acetylation and SIRT2 expression are shown. Our findings unravel involvement of SIRT5 and OGDH in metabolic adaptation to seizures through protein acylation, consistent with the known neuroprotective role of SIRT5 and contribution of OGDH to the Glu/GABA balance perturbed in epilepsy.
- Добавил в систему: Алешин Василий Алексеевич
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