The Expression and Localization of Histone Acetyltransferases HAT1 and PCAF in Neurons and Astrocytes of the Photothrombotic Stroke-Induced Penumbra in the Rat Brain Cortex

Stroke is one of the leading reasons of human death. Ischemic penumbra that surrounds the stroke-induced infarction core is potentially salvageable, but molecular mechanisms of its formation are poorly known. Histone acetylation induces chromatin decondensation and stimulates gene expression. We studied the changes in the levels and localization of histone acetyltransferases HAT1 and PCAF in penumbra after photothrombotic stroke (PTS, a stroke model). In PTS, laser irradiation induces local occlusion of cerebral vessels after photosensitization by Rose Bengal. HAT1 and PCAF are poorly expressed in normal cortical neurons and astrocytes, but they are overexpressed 4-24 h after PTS. Their predominant localization in neuronal nuclei did not change after PTS, but their levels in the astrocyte nuclei significantly increased. Western blotting showed the increase of HAT1 and PCAF levels in the cytoplasmic fraction of the PTS-induced penumbra. In the nuclear fraction, PCAF level did not change, and HAT1 was overexpressed only at 24 h post-PTS. PTS-induced upregulation of HAT1 and PCAF in the penumbra was mainly associated with overexpression in the cytoplasm of neurons and especially astrocytes. HAT1 and PCAF did not co-localize with TUNEL-positive cells that indicated their nonparticipation in PTS-induced apoptosis.

Keywords: Epigenetics; Histone acetyltransferase, HAT1, PCAF; Penumbra; Photothrombotic stroke.