Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia.
Int J Mol Sci. 2021 Jun 8;22(12):6179. doi: 10.3390/ijms22126179.
The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.
Semax（Met-Glu-His-Phe-Pro-Gly-Pro）肽是一种合成的黑色素皮质素衍生物，用于治疗缺血性中风。先前，使用大鼠脑缺血模型研究 Semax 作用的分子机制的研究表明，该肽增强了神经营养因子及其受体的转录，并调节了参与免疫反应的基因的表达。全基因组 RNA-Seq 分析表明，在大鼠短暂性大脑中动脉闭塞（tMCAO）模型中，Semax 抑制了炎症基因的表达并激活了神经递质基因的表达。在这里，我们旨在通过参与炎症和细胞死亡过程（MMP-9、c-Fos 和 JNK）的关键蛋白质以及中风的神经保护和恢复（CREB）的大脑表达谱来评估 tMCAO 后 24 小时 Semax 在该模型中的作用，我们观察到在皮质下结构（包括缺血损伤的焦点）中活性 CREB 的上调；在相邻的额顶叶皮质中 MMP-9 和 c-Fos 的下调；以及在两种组织中活性 JNK 的下调。此外，构建了一个调控网络。总之，炎症和细胞死亡过程的抑制以及恢复的激活可能有助于 Semax 在转录组和蛋白质水平上的神经保护作用。
