|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ИНХС РАН |
||
Acylation of the Rat Brain Proteins is Affected by the Inhibition of Pyruvate Dehydrogenase in vivoстатья
- Авторы: Aleshin Vasily A., Sibiryakina Daria A., Kazantsev Alexey V., Graf Anastasia V., Bunik Victoria I.
- Журнал: Biochemistry (Moscow)
- Том: 88
- Номер: 1
- Год издания: 2023
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 105
- Последняя страница: 118
- Оригинальные версии: Ацилирование белков мозга крысы изменяется при специфическом ингибировании пируватдегидрогеназы in vivo
- DOI: 10.1134/S0006297923010091
- Аннотация: Organism adaptation to metabolic challenges requires coupling of metabolism to gene expression. In this regard, acylations of histones and metabolic proteins acquire significant interest. We hypothesize that adaptive response to inhibition of a key metabolic process, catalyzed by the acetyl-CoA-generating pyruvate dehydrogenase (PDH) complex, is mediated by changes in the protein acylations. The hypothesis is tested by intranasal administration to animals of PDH-specific inhibitors acetyl(methyl)phosphinate (AcMeP) or acetylphosphonate methyl ester (AcPMe), followed by the assessment of physiological parameters, brain protein acylation, and expression/phosphorylation of PDHA subunit. At the same dose, AcMeP, but not AcPMe, decreases acetylation and increases succinylation of the brain proteins with apparent molecular masses of 15-20 kDa. Regarding the proteins of 30-50 kDa, a strong inhibitor AcMeP affects acetylation only, while a less efficient AcPMe mostly increases succinylation. The unchanged succinylation of the 30-50 kDa proteins after the administration of AcMeP coincides with the upregulation of desuccinylase SIRT5. No significant differences between the levels of brain PDHA expression, PDHA phosphorylation, parameters of behavior or ECG are observed in the studied animal groups. The data indicate that the short-term inhibition of brain PDH affects acetylation and/or succinylation of the brain proteins, that depends on the inhibitor potency, protein molecular mass, and acylation type. The homeostatic nature of these changes is implied by the stability of physiological parameters after the PDH inhibition.
- Добавил в систему: Алешин Василий Алексеевич