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The Peptide Drug ACTH(4–7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain

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Abstract

Due to its nootropic, neuroprotective, and immunomodulatory effects, the peptide Semax is utilized in the treatment of ischemic stroke. Our earlier RNA-Seq analysis of the transcriptome in an ischemic model of transient occlusion of the middle cerebral artery showed an increase in the mRNA levels of many proinflammatory genes, and the suppression of their induction by Semax. However, for many relevant genes, including Il1a, Il1b, Il6 and Tnfa, the levels of their expression were too low for detailed quantitative evaluation. Here we utilize qRT-PCR to analyze the effects of the Semax peptide on the expression of weakly expressed mRNAs encoding several proinflammatory mediators, and show that exposure to Semax leads to a statistically significant decrease in the Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNAs, which compensates for the increase in the transcription of these genes induced by ischemia-reperfusion. We conclude that the observed protective effect of Semax in the model of stroke may be due to its anti-inflammatory effects. We also discuss the limitations of the RNA-Seq when applied to quantifying less abundant transcripts as compared to the real-time RT-PCR method.

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Funding

The work was supported by the Russian Science Foundation, project no. 19-14-00268.

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Authors and Affiliations

  1. National Research Center “Kurchatov Institute”—Institute of Molecular Genetics, 123182, Moscow, Russia

    L. V. Dergunova, V. G. Dmitrieva, I. B. Filippenkov, V. V. Stavchansky, L. V. Valieva, O. Y. Sudarkina, N. F. Myasoedov & S. A. Limborska

  2. Pirogov Russian National Research Medical University, Moscow, Russian Federation; Federal Center of Cerebrovascular Pathology and Stroke, Ministry of Health Care of Russian Federation, 117342, Moscow, Russia

    A. E. Denisova & L. V. Gubsky

  3. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249031, Obninsk, Kaluga oblast, Russia

    V. V. Yuzhakov & L. E. Sevan’kaeva

Authors
  1. L. V. Dergunova
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  2. V. G. Dmitrieva
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  3. I. B. Filippenkov
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  4. V. V. Stavchansky
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  6. V. V. Yuzhakov
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  7. L. E. Sevan’kaeva
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  8. L. V. Valieva
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  9. O. Y. Sudarkina
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  10. L. V. Gubsky
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  11. N. F. Myasoedov
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  12. S. A. Limborska
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Corresponding author

Correspondence to L. V. Dergunova.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All procedures involving animals were performed in compliance with ethical standards of the facilities or established practices of such experiments.

Additional information

Translated by A. Deryabina

Abbreviations: ACTH, adrenocorticotropic hormone; DEGs, differentially expressed genes; MRI, magnetic resonance imaging; MCA, middle cerebral artery; 3D-TOF MRA, three-dimensional time-of-flight magnetic resonance angiography; ADC, apparent diffusion coefficient; Ct, amplification cycle threshold; DWI, diffusion-weighted imaging; FPKM, fragments per kilobase per million reads; PGP, Pro-Gly-Pro; pMCAO, permanent middle cerebral artery occlusion model; RNA-Seq, high throughput RNA sequencing; T2 WI, T2-weighted transverse image; tMCAO, transient middle cerebral artery occlusion model.

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Dergunova, L.V., Dmitrieva, V.G., Filippenkov, I.B. et al. The Peptide Drug ACTH(4–7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain. Mol Biol 55, 346–353 (2021). https://doi.org/10.1134/S0026893321010040

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