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Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.
Genes (Basel). 2020 06 22; 11(6)G

Abstract

Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions.

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Authors+Show Affiliations

Filippenkov IB
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Stavchansky VV
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Denisova AE
Pirogov Russian National Research Medical University, Federal Center of Cerebrovascular Pathology and Stroke, Ministry of Health Care of Russian Federation, 117342 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, 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, 249031 Obninsk, Russia.
Sudarkina OY
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Dmitrieva VG
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Gubsky LV
Pirogov Russian National Research Medical University, Federal Center of Cerebrovascular Pathology and Stroke, Ministry of Health Care of Russian Federation, 117342 Moscow, Russia.
Myasoedov NF
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Limborska SA
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.
Dergunova LV
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia.

MeSH

Adrenocorticotropic HormoneAnimalsBrainBrain IschemiaDisease Models, AnimalHumansInfarction, Middle Cerebral ArteryPeptide FragmentsRNA-SeqRatsReperfusion InjuryTranscriptome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32580520

Citation

Filippenkov, Ivan B., et al. "Novel Insights Into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats." Genes, vol. 11, no. 6, 2020.
Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6).
Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan'kaeva, L. E., Sudarkina, O. Y., Dmitrieva, V. G., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V. (2020). Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes, 11(6). https://doi.org/10.3390/genes11060681
Filippenkov IB, et al. Novel Insights Into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020 06 22;11(6) PubMed PMID: 32580520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. AU - Filippenkov,Ivan B, AU - Stavchansky,Vasily V, AU - Denisova,Alina E, AU - Yuzhakov,Vadim V, AU - Sevan'kaeva,Larisa E, AU - Sudarkina,Olga Y, AU - Dmitrieva,Veronika G, AU - Gubsky,Leonid V, AU - Myasoedov,Nikolai F, AU - Limborska,Svetlana A, AU - Dergunova,Lyudmila V, Y1 - 2020/06/22/ PY - 2020/05/16/received PY - 2020/06/09/revised PY - 2020/06/18/accepted PY - 2020/6/26/entrez PY - 2020/6/26/pubmed PY - 2021/3/19/medline KW - RNA-Seq KW - mRNA expression KW - peptide regulation KW - synthetic melanocortin derivative ACTH(4-7)PGP (Semax) KW - tMCAO JF - Genes JO - Genes (Basel) VL - 11 IS - 6 N2 - Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions. SN - 2073-4425 UR - https://www.unboundmedicine.com/medline/citation/32580520/Novel_Insights_into_the_Protective_Properties_of_ACTH_4_7_PGP__Semax__Peptide_at_the_Transcriptome_Level_Following_Cerebral_Ischaemia_Reperfusion_in_Rats_ DB - PRIME DP - Unbound Medicine ER -