Sirtuins, class III histone deacetylases, are involved in the regulation of tissue repair processes and brain functions after a stroke. The ability of some isoforms of sirtuins to circulate between the nucleus and cytoplasm may have various pathophysiological effects on the cells. In present work, we focused on the role of non-mitochondrial sirtuins SIRT1, SIRT2, and SIRT6 in the restoration of brain cells following ischemic stroke. Here, using a photothrombotic stroke (PTS) model in mice, we studied whether local stroke affects the level and intracellular localization of SIRT1, SIRT2, and SIRT6 in neurons and astrocytes of the intact cerebral cortex adjacent to the ischemic ipsilateral hemisphere and in the analogous region of the contralateral hemisphere at different time points during the recovery period after a stroke. We evaluated the co-localization of sirtuins with growth-associated protein-43 (GAP-43), the presynaptic marker synaptophysin (SYN) and acetylated α-tubulin (Ac-α-Tub), that are associated with brain plasticity and are known to be involved in brain repair after a stroke. The results show that during the recovery period, an increase in SIRT1 and SIRT2 levels occurred. The increase of SIRT1 level was associated with an increase in synaptic plasticity proteins, whereas the increase of SIRT2 level was associated with an acetylated of α-tubulin, that can reduce the mobility of neurites. SIRT6 co-localized with GAP-43, but not with SYN. Moreover, we showed that SIRT1, SIRT2, and SIRT6 are not involved in the PTS-induced apoptosis of penumbra cells. Taken together, our results suggest that sirtuins functions differ depending on cell type, intracellular localization, specificity of sirtuins isoforms to different substrates and nature of post-translational modifications of enzymes.

Sirtuins，III类组蛋白脱乙酰基酶，参与中风后组织修复过程和脑功能的调节。沉默调节蛋白的一些同工型在细胞核和细胞质之间循环的能力可能对细胞具有各种病理生理作用。在目前的工作中，我们集中于非线粒体sirtuins SIRT1，SIRT2和SIRT6在缺血性中风后脑细胞的恢复中的作用。在这里，我们使用小鼠的光血栓性中风（PTS）模型，研究局部中风是否会影响与缺血同侧半球相邻的完整大脑皮层的神经元和星形胶质细胞中SIRT1，SIRT2和SIRT6的水平和细胞内定位。脑卒中恢复期在不同时间点的对侧半球区域。我们评估了sirtuins与生长相关蛋白43（GAP-43），突触前标记突触素（SYN）和乙酰化α-微管蛋白（Ac-α-Tub）的共定位性，它们与脑可塑性相关，并且是已知的中风后要进行脑修复。结果表明，在恢复期间，SIRT1和SIRT2的水平增加了。SIRT1水平的增加与突触可塑性蛋白的增加有关，而SIRT2水平的增加与α-微管蛋白的乙酰化有关，这可以减少神经突的活动性。SIRT6与GAP-43共定位，但与SYN不共定位。此外，我们显示SIRT1，SIRT2和SIRT6不参与PTS诱导的半影细胞凋亡。综上所述，我们的结果表明，沉默调节蛋白的功能因细胞类型而异，