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Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats.
Mol Genet Genomics. 2017 Jun; 292(3):635-653.MG

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Medvedeva EV
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. medvedevaekaterina@yandex.ru.
Dmitrieva VG
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
Limborska SA
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. Pirogov Russian National Research Medical University, Ministry of Health, Moscow, 117997, Russia.
Myasoedov NF
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
Dergunova LV
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. Pirogov Russian National Research Medical University, Ministry of Health, Moscow, 117997, Russia.

MeSH

Adrenocorticotropic HormoneAnimalsAntigen PresentationBrain IschemiaDisease Models, AnimalGene Expression ProfilingGenes, Immunoglobulin Heavy ChainImmunoglobulin Heavy ChainsMaleMiddle Cerebral ArteryNeuroprotective AgentsOligopeptidesPeptide FragmentsProlineRatsRats, WistarStress, PhysiologicalTranscriptome

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28255762

Citation

Medvedeva, Ekaterina V., et al. "Semax, an Analog of ACTH(4-7), Regulates Expression of Immune Response Genes During Ischemic Brain Injury in Rats." Molecular Genetics and Genomics : MGG, vol. 292, no. 3, 2017, pp. 635-653.
Medvedeva EV, Dmitrieva VG, Limborska SA, et al. Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. Mol Genet Genomics. 2017;292(3):635-653.
Medvedeva, E. V., Dmitrieva, V. G., Limborska, S. A., Myasoedov, N. F., & Dergunova, L. V. (2017). Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. Molecular Genetics and Genomics : MGG, 292(3), 635-653. https://doi.org/10.1007/s00438-017-1297-1
Medvedeva EV, et al. Semax, an Analog of ACTH(4-7), Regulates Expression of Immune Response Genes During Ischemic Brain Injury in Rats. Mol Genet Genomics. 2017;292(3):635-653. PubMed PMID: 28255762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. AU - Medvedeva,Ekaterina V, AU - Dmitrieva,Veronika G, AU - Limborska,Svetlana A, AU - Myasoedov,Nikolay F, AU - Dergunova,Lyudmila V, Y1 - 2017/03/02/ PY - 2016/07/12/received PY - 2017/02/07/accepted PY - 2017/3/4/pubmed PY - 2017/8/5/medline PY - 2017/3/4/entrez KW - ACTH analog KW - Cerebral ischemia model KW - Genome-wide transcriptome analysis KW - Immune response KW - Neuroprotective regulatory peptides KW - Pro-Gly-Pro KW - Semax SP - 635 EP - 653 JF - Molecular genetics and genomics : MGG JO - Mol Genet Genomics VL - 292 IS - 3 N2 - 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. SN - 1617-4623 UR - https://www.unboundmedicine.com/medline/citation/28255762/Semax_an_analog_of_ACTH_4_7__regulates_expression_of_immune_response_genes_during_ischemic_brain_injury_in_rats_ L2 - https://doi.org/10.1007/s00438-017-1297-1 DB - PRIME DP - Unbound Medicine ER -