Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats
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<sub>(4-7)</sub>PGP (Semax), has been used successfully in the tr...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/11/6/681 |
| _version_ | 1797564428488540160 |
|---|---|
| author | Ivan B. Filippenkov Vasily V. Stavchansky Alina E. Denisova Vadim V. Yuzhakov Larisa E. Sevan’kaeva Olga Y. Sudarkina Veronika G. Dmitrieva Leonid V. Gubsky Nikolai F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova |
| author_facet | Ivan B. Filippenkov Vasily V. Stavchansky Alina E. Denisova Vadim V. Yuzhakov Larisa E. Sevan’kaeva Olga Y. Sudarkina Veronika G. Dmitrieva Leonid V. Gubsky Nikolai F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova |
| author_sort | Ivan B. Filippenkov |
| collection | DOAJ |
| description | 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<sub>(4-7)</sub>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. |
| first_indexed | 2024-03-10T18:57:12Z |
| format | Article |
| id | doaj.art-4c4c777741c1402bb0f0c69164154a6d |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T18:57:12Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-4c4c777741c1402bb0f0c69164154a6d2023-11-20T04:38:49ZengMDPI AGGenes2073-44252020-06-0111668110.3390/genes11060681Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in RatsIvan B. Filippenkov0Vasily V. Stavchansky1Alina E. Denisova2Vadim V. Yuzhakov3Larisa E. Sevan’kaeva4Olga Y. Sudarkina5Veronika G. Dmitrieva6Leonid V. Gubsky7Nikolai F. Myasoedov8Svetlana A. Limborska9Lyudmila V. Dergunova10Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaPirogov Russian National Research Medical University, Federal Center of Cerebrovascular Pathology and Stroke, Ministry of Health Care of Russian Federation, 117342 Moscow, RussiaA. Tsyb Medical Radiological Research Center–Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249031 Obninsk, RussiaA. Tsyb Medical Radiological Research Center–Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249031 Obninsk, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaPirogov Russian National Research Medical University, Federal Center of Cerebrovascular Pathology and Stroke, Ministry of Health Care of Russian Federation, 117342 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, RussiaCerebral 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<sub>(4-7)</sub>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.https://www.mdpi.com/2073-4425/11/6/681tMCAOmRNA expressionRNA-Seqsynthetic melanocortin derivative ACTH<sub>(4-7)</sub>PGP (Semax)peptide regulation |
| spellingShingle | Ivan B. Filippenkov Vasily V. Stavchansky Alina E. Denisova Vadim V. Yuzhakov Larisa E. Sevan’kaeva Olga Y. Sudarkina Veronika G. Dmitrieva Leonid V. Gubsky Nikolai F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats Genes tMCAO mRNA expression RNA-Seq synthetic melanocortin derivative ACTH<sub>(4-7)</sub>PGP (Semax) peptide regulation |
| title | Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats |
| title_full | Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats |
| title_fullStr | Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats |
| title_full_unstemmed | Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats |
| title_short | Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats |
| title_sort | novel insights into the protective properties of acth sub 4 7 sub pgp semax peptide at the transcriptome level following cerebral ischaemia reperfusion in rats |
| topic | tMCAO mRNA expression RNA-Seq synthetic melanocortin derivative ACTH<sub>(4-7)</sub>PGP (Semax) peptide regulation |
| url | https://www.mdpi.com/2073-4425/11/6/681 |
| work_keys_str_mv | AT ivanbfilippenkov novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT vasilyvstavchansky novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT alinaedenisova novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT vadimvyuzhakov novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT larisaesevankaeva novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT olgaysudarkina novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT veronikagdmitrieva novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT leonidvgubsky novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT nikolaifmyasoedov novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT svetlanaalimborska novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats AT lyudmilavdergunova novelinsightsintotheprotectivepropertiesofacthsub47subpgpsemaxpeptideatthetranscriptomelevelfollowingcerebralischaemiareperfusioninrats |