Brain Protein Expression Profile Confirms the Protective Effect of the ACTH
Adrenocorticotropic Hormone
/ analogs & derivatives
Animals
Brain
/ drug effects
Brain Ischemia
/ metabolism
Disease Models, Animal
Male
Neuroprotective Agents
/ pharmacology
Peptide Fragments
/ pharmacology
Proteome
/ drug effects
RNA-Seq
Rats
Rats, Wistar
Reperfusion Injury
/ metabolism
Transcriptome
/ drug effects
ACTH(4–7)PGP (Semax)
gene and protein expression profile
immunodetection
ischemic stroke
real-time RT-PCR
spreading depression
tMCAO
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
08 Jun 2021
08 Jun 2021
Historique:
received:
26
04
2021
revised:
02
06
2021
accepted:
05
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
27
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34201112
pii: ijms22126179
doi: 10.3390/ijms22126179
pmc: PMC8226508
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Peptide Fragments
0
Proteome
0
ACTH (4-7), Pro-Gly-Pro-
80714-61-0
Adrenocorticotropic Hormone
9002-60-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Russian Science Foundation
ID : 19-14-00268
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