Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave, Rostov-on-Don, 344090, Russia.
Mol Neurobiol. 2020 Jul;57(7):3219-3227. doi: 10.1007/s12035-020-01959-6. Epub 2020 Jun 6.
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.
中风是人类死亡的主要原因之一。围绕中风引起的梗塞核心的缺血半影区具有潜在的可挽救性，但其形成的分子机制知之甚少。组蛋白乙酰化诱导染色质解凝聚并刺激基因表达。我们研究了光血栓性中风（PTS，中风模型）后半影区中组蛋白乙酰转移酶 HAT1 和 PCAF 的水平和定位变化。在 PTS 中，激光照射在 Rose Bengal 光敏化后诱导脑血管局部闭塞。HAT1 和 PCAF 在正常皮质神经元和星形胶质细胞中表达水平较低，但在 PTS 后 4-24 小时表达上调。它们在神经元核中的主要定位在 PTS 后没有改变，但在星形胶质细胞核中的水平显著增加。Western blot 显示 PTS 诱导的半影区细胞质部分 HAT1 和 PCAF 水平增加。在核部分，PCAF 水平没有变化，只有在 PTS 后 24 小时 HAT1 过度表达。PTS 诱导的半影区中 HAT1 和 PCAF 的上调主要与神经元特别是星形胶质细胞中细胞质的过度表达有关。HAT1 和 PCAF 与 TUNEL 阳性细胞不共定位，表明它们不参与 PTS 诱导的细胞凋亡。
