title: Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats.
abstract: Brain stroke continues to claim the lives of million people every year. To build the effective strategies for stroke treatment it is necessary to understand the neuroprotective mechanisms that are able to prevent the ischemic injury. Consisting of the ACTH(4-7)fragment and the tripeptide Pro-Gly-Pro (PGP), the synthetic peptide Semax effectively protects brain against ischemic stroke. However, the molecular mechanisms underlying its neuroprotection and participation of PGP in them are still needed to be clarified. To reveal biological processes and signaling pathways, which are affected by Semax and PGP, we performed the transcriptome analysis of cerebral cortex of rats with focal cerebral ischemia treated by these peptides. The genome-wide biochip data analysis detected the differentially expressed genes (DEGs) and bioinformatic web-tool Ingenuity iReport found DEGs associations with several biological processes and signaling pathways. The immune response is the process most markedly affected by the peptide: Semax enhances antigen presentation signaling pathway, intensifies the effect of ischemia on the interferon signaling pathways and affects the processes for synthesizing immunoglobulins. Semax significantly increased expression of the gene encoding the immunoglobulin heavy chain, highly affects on cytokine, stress response and ribosomal protein-encoding genes after occlusion. PGP treatment of rats with ischemia attenuates the immune activity and suppresses neurotransmission in the CNS. We suppose that neuroprotective mechanism of Semax is realized via the neuroimmune crosstalk, and the new properties of PGP were found under ischemia. Our results provided the basis for further proteomic investigations in the field of searching Semax neuroprotection mechanism.
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. medvedevaekaterina@yandex.ru.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Medvedeva
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
authors.forename: Veronika G
authors.initials: VG
authors.lastname: Dmitrieva
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.|Pirogov Russian National Research Medical University, Ministry of Health, Moscow, 117997, Russia.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Limborska
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
authors.forename: Nikolay F
authors.initials: NF
authors.lastname: Myasoedov
authors.affiliation: Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.|Pirogov Russian National Research Medical University, Ministry of Health, Moscow, 117997, Russia.
authors.forename: Lyudmila V
authors.initials: LV
authors.lastname: Dergunova
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D002545:Brain Ischemia / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D050438:Genes, Immunoglobulin Heavy Chain / Q000187:drug effects*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D020768:Middle Cerebral Artery / Q000601:surgery; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects / Q000276:immunology; D059467:Transcriptome / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; C113164:prolyl-glycyl-proline; C048487:ACTH (4-7), Pro-Gly-Pro-; D000324:Adrenocorticotropic Hormone; D011392:Proline
keywords: ACTH analog; Cerebral ischemia model; Genome-wide transcriptome analysis; Immune response; Neuroprotective regulatory peptides; Pro-Gly-Pro; Semax