Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke.

Autor: Guzenko VV; Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia., Bachurin SS; Department of General and Clinical Biochemistry no.2, Rostov State Medical University, Nakhichevansky lane, Rostov-on-Don, 344022, Russia., Khaitin AM; Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia., Dzreyan VA; Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia., Kalyuzhnaya YN; Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia., Bin H; State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China., Demyanenko SV; Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia. svdemyanenko@sfedu.ru.; Department of General and Clinical Biochemistry no.2, Rostov State Medical University, Nakhichevansky lane, Rostov-on-Don, 344022, Russia. svdemyanenko@sfedu.ru.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2024 Oct; Vol. 15 (5), pp. 970-985. Date of Electronic Publication: 2023 Aug 15.
DOI: 10.1007/s12975-023-01183-z
Abstrakt: p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynamic regulation of the acetylation of p53 at lysine 320 is controlled by acetyltransferase PCAF and histone deacetylases HDAC1 and HDAC6. The in silico simulation have made it possible to suggest the acetylation of p53 at lysine 320 acetylation may facilitate the shuttling of p53 between the nucleus and cytoplasm in penumbra neurons. Acetylation of p53 at lysine 320 is more preferable than acetylation at lysine 373 and probably promotes survival and repair of penumbra neurons after stroke. Strategies to increase p53 acetylation at lysine 320 via increasing PCAF activity, inhibiting HDAC1 or HDAC6, inhibiting p53, or a combination of these interventions may have therapeutic benefits for stroke recovery and would be promising for neuroprotective therapy of stroke.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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