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Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.
Int J Mol Sci. 2021 Jun 08; 22(12)IJ

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.

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Authors+Show Affiliations

Sudarkina OY
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Filippenkov IB
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Stavchansky VV
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Denisova AE
Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia.
Yuzhakov VV
A. Tsyb Medical Radiological Research Center-Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Zhukov st. 10, 249031 Obninsk, Russia.
Sevan'kaeva LE
A. Tsyb Medical Radiological Research Center-Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Zhukov st. 10, 249031 Obninsk, Russia.
Valieva LV
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Remizova JA
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Dmitrieva VG
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Gubsky LV
Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia. Federal Center for the Brain and Neurotechnologies, Federal Biomedical Agency, Ostrovitianov str. 1, Building 10, 117997 Moscow, Russia.
Myasoedov NF
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Limborska SA
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.
Dergunova LV
Institute of Molecular Genetics of National Research Center Kurchatov Institute, Kurchatov Sq. 2, 123182 Moscow, Russia.

MeSH

Adrenocorticotropic HormoneAnimalsBrainBrain IschemiaDisease Models, AnimalMaleNeuroprotective AgentsPeptide FragmentsProteomeRNA-SeqRatsRats, WistarReperfusion InjuryTranscriptome

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34201112

Citation

Sudarkina, Olga Yu, et al. "Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion." International Journal of Molecular Sciences, vol. 22, no. 12, 2021.
Sudarkina OY, Filippenkov IB, Stavchansky VV, et al. Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. Int J Mol Sci. 2021;22(12).
Sudarkina, O. Y., Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan'kaeva, L. E., Valieva, L. V., Remizova, J. A., Dmitrieva, V. G., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2021). Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. International Journal of Molecular Sciences, 22(12). https://doi.org/10.3390/ijms22126179
Sudarkina OY, et al. Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. Int J Mol Sci. 2021 Jun 8;22(12) PubMed PMID: 34201112.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. AU - Sudarkina,Olga Yu, AU - Filippenkov,Ivan B, AU - Stavchansky,Vasily V, AU - Denisova,Alina E, AU - Yuzhakov,Vadim V, AU - Sevan'kaeva,Larisa E, AU - Valieva,Liya V, AU - Remizova,Julia A, AU - Dmitrieva,Veronika G, AU - Gubsky,Leonid V, AU - Myasoedov,Nikolai F, AU - Limborska,Svetlana A, AU - Dergunova,Lyudmila V, Y1 - 2021/06/08/ PY - 2021/04/26/received PY - 2021/06/02/revised PY - 2021/06/05/accepted PY - 2021/7/2/entrez PY - 2021/7/3/pubmed PY - 2021/7/27/medline KW - ACTH(4–7)PGP (Semax) KW - gene and protein expression profile KW - immunodetection KW - ischemic stroke KW - real-time RT-PCR KW - spreading depression KW - tMCAO JF - International journal of molecular sciences JO - Int J Mol Sci VL - 22 IS - 12 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/34201112/Brain_Protein_Expression_Profile_Confirms_the_Protective_Effect_of_the_ACTH_4_7_PGP_Peptide__Semax__in_a_Rat_Model_of_Cerebral_Ischemia_Reperfusion_ DB - PRIME DP - Unbound Medicine ER -