E2F1 acetylation regulates apoptosis of perifocal region cells after photothrombotic stroke
Valeria V. Guzenko, Yuliya N. Kalyuzhnaya, Svetlana V. Demyanenko
Southern Federal University, Rostov‐on‐Don, Russia
Abstract
We studied the interaction of E2F1 with different isoforms of histone acetyltransferases in neurons of the perifocal region at 4 and 24 hours after photothrombotic stroke (PTS) in rats. Photothrombotic stroke (PTS) was induced in the rat cortex after intravenous injection of photosensitizer Rose Bengal (20 mg/kg), followed by laser irradiation of the sensorimotor cortex (532 nm, 60 mW/cm2, Ø3 mm, 30 min). PTS caused increased E2F1 acetylation as early as 24 h and even 4 h after irradiation of rat brain. Immunofluorescence microscopy, Duolink® proximity ligation assay (PLA®) and co-immunoprecipitation showed the interaction of E2F1 with histone acetyltransferase PCAF (p300/CBP-associated), also known as KAT2B. To evaluate whether this transcription factor promotes cell apoptosis, we examined the effect of pharmacological inhibition of E2F activity by HLM006474 (100 mg/kg, intraperitoneally) following PTS. A high level of E2F1 acetylation was in apoptotically proficient cells. It has been shown that E2F1 acetylation increases the stability and proapoptotic activity of E2F1 in the perifocal region neurons.
The study was supported by the Russian Science Foundation (grant No. 21-15-00188).
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Svetlana Demyanenko
Southern Federal University
Russia
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