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Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke

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Abstract

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.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Russian Science Foundation (Grant number 21-15-00188).

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Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachki ave., Rostov-on-Don, 344090, Russia

    V.V. Guzenko, A.M. Khaitin, V.A. Dzreyan, Y.N. Kalyuzhnaya & S.V. Demyanenko

  2. Department of General and Clinical Biochemistry no.2, Rostov State Medical University, Nakhichevansky lane, Rostov-on-Don, 344022, Russia

    S.S. Bachurin & S.V. Demyanenko

  3. 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

    He Bin

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Contributions

Guzenko V.V.—surgery, Western Blot analysis, Co-IP, Duoling PLA, immunohistochemistry; Bachurin S.S. —MDS; Khaitin A.M.—statistical processing, figures, writing; Dzreyan V.A.—Western Blot Analysis, Co-IP, immunoprecipitation, Duolink PLA; Kalyuzhnaya Y.N.—surgery, immunohistochemistry; He Bin—conceptualization, MDS, writing; Demyanenko S.V.—surgery, immunohistochemistry, supervision, conceptualization, funding acquisition, writing.

Corresponding author

Correspondence to S.V. Demyanenko.

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Ethics Approval

The study has followed all the applicable standards, including international, national, and institutional guidelines for keeping and using laboratory animals. All experimental procedures were carried out in accordance with the European Union guidelines 86/609/ЕЕС for the use of experimental animals and local legislation for ethics of experiments on animals. The animal protocols were evaluated and approved by the Animal Care and Use Committee of the Southern Federal University (Approval No 3-14/2014; 08/2016 and 02/2022).

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Guzenko, V., Bachurin, S., Khaitin, A. et al. Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01183-z

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