Skip to main content
Log in

The Administration of Semax and HLDF-6 Peptides to Rats Regulates Protein Synthesis Rhythm in Hepatocytes and Corrects Senescent Disturbances

  • DEVELOPMENTAL BIOLOGY OF ANIMALS (INVERTEBRATE AND VERTEBRATE)
  • Published:
Russian Journal of Developmental Biology Aims and scope Submit manuscript

Abstract

To clarify the organizing effect of Semax and HLDF-6 peptides on the kinetics of protein synthesis in hepatocytes, in addition to an in vitro study (Brodsky et al., 2019), the effects of these peptides in vivo have been studied. The circahoralian (ultradian) rhythm of protein synthesis, that is, a marker of the direct cell-to-cell communication, was investigated in rats of different ages. Peptides were injected intraperitoneally into young (2–3-month-old) or old (1.5–2-year-old) rats at a 50–100-µg/kg dose. Hepatocytes were isolated and sparse or dense cultures were established. In sparse cultures from young rats that received one or another peptide, the rhythm of protein synthesis was observed; in the cultures from rats of the same age that were injected with saline, no rhythm was found. In dense cultures of old rats after the action of the peptide, the amplitudes of the rhythm of protein synthesis did not differ from the rhythms observed in young rats; after saline injection, the rhythm amplitudes were twice as low. Injection of the peptide into adult rats that had previously received dopamine caused a protein synthesis rhythm characteristic for rats of this age; the administration of dopamine abolished the rhythm. The synchronizing effect of the peptides was maintained for at least 2 days after their single administration to the rat. The use of Semax or HLDF-6 is recommended to compensate for the disturbances of the kinetics of protein synthesis in humans in aging and pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.

Similar content being viewed by others

REFERENCES

  1. Bogachouk, A.P., Storozheva, Z.I., Solovjeva, O.A., Sherstnev, V.V., Zolotarev, Y.A., Azev, V.N., Rodionov, I.L., Surina, E.A., and Lipkin, V.M., Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the hldf-6 peptide in animal models of Alzheimer’s disease, Psychopharmacology, 2016, vol. 30, no. 1, pp. 78–92.

    Article  CAS  Google Scholar 

  2. Brodsky, V.Y., Circahoralian (ultradian) metabolic rhythms, Biochemistry (Moscow), 2014, vol. 79, no. 6, pp. 483–495.

    CAS  PubMed  Google Scholar 

  3. Brodsky, V.Y., Biochemistry of direct cell–cell interactions. Signaling factors regulating orchestration of cell populations, Biochemistry (Moscow), 2018, vol. 83, no. 8, pp. 890–906.

    CAS  PubMed  Google Scholar 

  4. Brodsky, V.Y., Nechaeva, N.V., Terskikh, V.V., Novikova, T.E., Gvazava, I.G., and Fateeva, V.I., A serum-free medium that preserves normal morphology and a high level of protein synthesis in hepatocytes, Biol. Bull. (Moscow), 1996, vol. 23, no. 4, pp. 323–326.

    Google Scholar 

  5. Brodsky, V.Y., Konchenko, D.S., Zvezdina, N.D., Malchenko, L.A., and Dubovaja, T.K., Unlike norepinephrine and serotonin, dopamine disorganizes direct cell-cell communication in hepatocyte cultures, J. Cell Tissue Res., 2012, vol. 12, pp. 3265–3271.

    CAS  Google Scholar 

  6. Brodsky, V.Y., Zolotarev, Yu.A., Mal’chenko, L.A., Andreeva, L.A., Lazarev, D.S., Butorina, N.N., Kozik, V.S., and Myasoedov, N.F., Neiroprotektornye peptidy reguliruyut kinetiku sinteza belka v gepatotsitakh krys raznogo vozrasta, Russ. J. Dev. Biol., 2019, vol. 50, no. 5, pp. 268–275.

    Article  CAS  Google Scholar 

  7. Dmitrieva, V.G., Povarova, O.V., Skvortsova, V.I., Limborska, S.A., Myasoedov, N.F., and Dergunova, L.V., Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia, Cell Mol. Neurobiol., 2010, vol. 30, no. 1, pp. 71–79.

    Article  CAS  Google Scholar 

  8. Gambaryan, P.P. and Dukel’skaya, N.M., Krysa (Rat), Moscow: Sovetskaya Nauka, 1955.

    Google Scholar 

  9. Levitskaya, N.G., Glazova, N.Yu., Sebentsova, E.A., Manchenko, D.M., Vilenskii, D.A., Andreeva, L.A., Kamenskii, A.A., and Myasoedov, N.F., Investigation of the spectrum of physiological activities of the heptapeptide Semax, an ACTH4–10 analogue, Neurochem. J., 2008, vol. 2, nos. 1–2, pp. 95–101.

    Google Scholar 

  10. Levitskaya, N.G., Vilenskii, D.A., Sebentsova, E.A., Andreeva, L.A., Kamenskii, A.A., and Myasoedov, N.F., Influence of Semax on the emotional state of white rats in the norm and against the background of cholecystokinin-tetrapeptide action, Biol. Bull. (Moscow), 2010, vol. 37, no. 2, pp. 186–192.

    Article  CAS  Google Scholar 

  11. Myasoedov, N.F. and Grivennikov, I.A., Neuropeptides and their analogues in the regulation of functions of the nervous system of mammals, including humans: from the synthesis and study of the mechanisms of their action to creating a new generation of drugs, in Problemy i perspektivy molekulyarnoi genetiki (Problems and Prospects of Molecular Genetics), Moscow: Nauka, 2004, vol. 2, pp. 195–236.

  12. Neirodegenerativnye zabolevaniya: ot genoma do tselostnogo organizma (Neurodegenerative Diseases: From the Genome to the Whole Organism), Ugrumov, M.V., Ed., Moscow: Nauchnyi Mir, 2014.

    Google Scholar 

  13. Vasileva, E.V., Zolotarev, Yu.A., and Kovalev, G.I., The effects of nootropic drugs on metabotropic glutamate receptors in the brains of BALB/c and C57BL/6 mice, Neurochem. J., 2013, vol. 7, no. 2, pp. 128–134.

    Article  CAS  Google Scholar 

  14. Zolotarev, Yu.A., Kovalev, G.I., Dadayan, A.K., Kozik, V.S., Kondrakhin, E.A., Vasileva, E.V., and Lipkin, V.M., Investigation of the pharmacokinetics and pharmacodynamics of the amide form of the neuroprotective peptide HLDF-6 using compounds uniformly labeled with hydrogen isotopes, in Neirodegenerativnye zabolevaniya: ot genoma do tselostnogo organizma (Neurodegenerative Diseases: From the Genome to the Whole Organism), Ugrumov, M.V., Ed., Nauchnyi Mir, 2014, pp. 763–777.

  15. Zolotarev, Y.A., Kovalev, G.I., Kost, N.V., Voevodina, M.E., Sokolov, O.Y., Dadayan, A.K., Kondrakhin, E.A., Vasileva, E.V., Bogachuk, A.P., Azev, V.N., Lipkin, V.M., and Myasoedov, N.F., Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice, J. Psychopharmacol., 2016, vol. 30, no. 9, pp. 922–935.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGEMENTS

We are grateful to the Koltsov Institute of Developmental Biology, Russian Academy of Sciences, for providing access to the equipment.

Funding

This study was supported by the Russian Foundation for Basic Research (project no. 17-04-00460) and the state program according to the academic research plan of the Institute of Molecular Genetics of the Russian Academy of Sciences (project no. АААА-А19-119022590101-1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. Y. Brodsky.

Ethics declarations

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

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Translated by I. Matiulko

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brodsky, V.Y., Zolotarev, Y.A., Malchenko, L.A. et al. The Administration of Semax and HLDF-6 Peptides to Rats Regulates Protein Synthesis Rhythm in Hepatocytes and Corrects Senescent Disturbances. Russ J Dev Biol 51, 99–105 (2020). https://doi.org/10.1134/S1062360420020034

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062360420020034

Keywords:

Navigation