Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.

Abstract

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.

• Authors: Olga Yu Sudarkina, Ivan B Filippenkov, Vasily V Stavchansky, Alina E Denisova, Vadim V Yuzhakov, Larisa E Sevan'kaeva, Liya V Valieva, Julia A Remizova, Veronika G Dmitrieva, Leonid V Gubsky, Nikolai F Myasoedov, Svetlana A Limborska, Lyudmila V Dergunova
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 12 (Jun 08 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34201112 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Peptide Fragments
• Proteome
• ACTH (4-7), Pro-Gly-Pro-
• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (analogs & derivatives, pharmacology)
• Animals
• Brain (drug effects, metabolism)
• Brain Ischemia (metabolism, pathology, prevention & control)
• Disease Models, Animal
• Male
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (pharmacology)
• Proteome (drug effects)
• RNA-Seq
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Transcriptome (drug effects)