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.