| Autor: |
Stavchansky VV; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Filippenkov IB; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Remizova JA; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Denisova AE; Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, Russia., Mozgovoy IV; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Gubsky LV; Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, Russia.; Federal Center for the Brain and Neurotechnologies, Federal Biomedical Agency, Ostrovitianov Str. 1, Building 10, Moscow 117997, Russia., Myasoedov NF; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Andreeva LA; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Limborska SA; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia., Dergunova LV; Institute of Molecular Genetics of National Research Center 'Kurchatov Institute', Kurchatov Sq. 2, Moscow 123182, Russia. |
| Abstrakt: |
Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which includes Met-Glu-His-Phe (MEHF) fragments of adrenocorticotropic hormone and the C-terminal tripeptide PGP, serves as a neuroprotective drug for the treatment of ischemic stroke. Previously, we revealed that Semax mostly prevented the disruption of the gene expression pattern 24 h after a transient middle cerebral artery occlusion (tMCAO) in a rat brain model. The genes of this pattern were grouped into an inflammatory cluster (IC) and a neurotransmitter cluster (NC). Here, using real-time RT-PCR, the effect of other PGP-containing peptides, PGP and Pro-Gly-Pro-Leu (PGPL), on the expression of a number of genes in the IC and NC was studied 24 h after tMCAO. Both the PGP and PGPL peptides showed Semax-unlike effects, predominantly without changing gene expression 24 h after tMCAO. Moreover, there were IC genes ( iL1b , iL6 , and Socs3 ) for PGP, as well as IC ( iL6 , Ccl3 , Socs3 , and Fos ) and NC genes ( Cplx2 , Neurod6 , and Ptk2b ) for PGPL, that significantly changed in expression levels after peptide administration compared to Semax treatment under tMCAO conditions. Furthermore, gene enrichment analysis was carried out, and a regulatory gene network was constructed. Thus, the spectra of the common and unique effects of the PGP, PGPL, and Semax peptides under ischemia-reperfusion were distinguished. |
