Effect of glyprolines on the level of apoptotic and neurotrophic factors under conditions of “social” stress

Cover Page

Cite item

Full Text

Abstract

The aim of the article was to study the effect of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu, on the level of apoptotic factors (caspase-3, caspase-8, the tumor necrosis factor) and neurotrophic factors (the nerve growth factor and the brain neurotrophic factor) in the blood serum of white rats under the experimental modeling of “social” stress.

Materials and methods. The experimental studies were carried out on 90 nonlinear white male rats aged 6 months. By the type of behavior, in the process of “social” stress modeling, all the rats were divided into “aggressors” and “victims”. In the study, the following experimental groups (n=10) were formed: control individuals; groups of the rats exposed to stress for 20 days; groups of the animals treated intraperitoneally at the dose of 100 μg/kg/day, starting from the 1st day of the stress factor exposure, with a course of 20 days of glyproline compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu. The effect of the compounds on the level of apoptotic and neurotrophic factors was assessed by determining the level of caspase-3, caspase-8, the tumor necrosis factor, the nerve growth factor and the brain neurotrophic factor of white rat blood serum by enzyme immunoassay.

Results. According to the results of the study, it was found out that under the conditions of “social” stress, there was an increase in the apoptotic processes accompanied by an increase in the level of caspase-3, caspase-8, TNF-α in the blood serum of white rats, as well as a decrease in the concentration of neurotrophic factors – BDNF and NGF. The administration of giproline compounds against the background of stress, contributed to the restoration of the studied indicators level, which is most likely due to the presence of antiapoptotic and neuroprotective effects in giprolines due to the inhibition of the caspase-dependent cascade of apoptosis reactions, as well as the induction of the synthesis of neurotrophic factors with the antiapoptotic activity.

Conclusion. Thus, the administration of glyproline neuropeptide compounds Thr–Lys–Pro–Arg–Pro–Gly–Pro (Selank), Pro–Gly–Pro and Pro–Gly–Pro–Leu under stress conditions, contributes to the restoration of the initiating and effector caspases level, as well as of neurotrophic factors. As a result of the experiment, an anti-apoptotic effect is observed due to the inhibition of the caspase-dependent cascade of reactions, as well as a stress-protective effect is observed due to the restoration of the brain neurotrophic factors level.

About the authors

Anna L. Yasenyavskaya

Astrakhan State Medical University

Email: yasen_9@mail.ru
ORCID iD: 0000-0003-2998-2864

Candidate of Sciences, (Medicine), Head of the Research Establishment, Associate Professor of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Alexandra A. Tsibizova

Astrakhan State Medical University

Email: sasha3633@yandex.ru
ORCID iD: 0000-0002-9994-4751

Candidate of Sciences (Pharmacy), Associate Professor, Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Liudmila A. Andreeva

Institute of Molecular Genetics of National Research Centre "Kurchatov Institute"

Author for correspondence.
Email: landr@img.ras.ru
ORCID iD: 0000-0002-3927-8590

Sector Leader

Russian Federation, 2, Academician Kurchatov Square, Moscow, Russia, 123182

Nikolai F. Myasoedov

Institute of Molecular Genetics of National Research Centre "Kurchatov Institute"

Email: nfm@img.ras.ru
ORCID iD: 0000-0003-1294-102X

Doctor of Sciences (Chemistry), Professor, Academician of the Russian Academy of Sciences

Russian Federation, 2, Academician Kurchatov Square, Moscow, Russia, 123182

Olga A. Bashkina

Astrakhan State Medical University

Email: bashkina1@mail.ru
ORCID iD: 0000-0003-4168-4851

Doctor of Sciences (Medicine), Professor, Head of the Department of Pediatrics Faculty

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

Marina A. Samotrueva

Astrakhan State Medical University

Email: ms1506@mail.ru
ORCID iD: 0000-0001-5336-4455

Doctor of Sciences (Medicine), Professor, Head of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121, Bakinskaya Str., Astrakhan, Russia, 414000

References

  1. Benham G, Charak R. Stress and sleep remain significant predictors of health after controlling for negative affect. Stress Health. 2019 Feb;35(1):59–68. doi: 10.1002/smi.2840.
  2. Cohen S, Gianaros PJ, Manuck SB. A Stage Model of Stress and Disease. Perspect Psychol Sci. 2016 Jul;11(4):456–63. doi: 10.1177/1745691616646305.
  3. Magariños AM, Schaafsma SM, Pfaff DW. Impacts of stress on reproductive and social behaviors. Front Neuroendocrinol. 2018 Apr;49:86–90. doi: 10.1016/j.yfrne.2018.01.002.
  4. O’Connor DB, Thayer JF, Vedhara K. Stress and Health: A Review of Psychobiological Processes. Annu Rev Psychol. 2021 Jan 4;72:663–88. doi: 10.1146/annurev-psych-062520-122331.
  5. Mayboroda AA. Apoptoz: geny i belki [Apoptosis: genes and proteins]. Siberian medical journal. 2013; 3: 130–5. Russian
  6. Obeng E. Apoptosis (programmed cell death) and its signals – A review. Braz J Biol. 2021 Oct-Dec;81(4):1133–43. doi: 10.1590/1519-6984.228437.
  7. Park C, Rosenblat JD, Brietzke E, Pan Z, Lee Y, Cao B, Zuckerman H, Kalantarova A, McIntyre RS. Stress, epigenetics and depression: A systematic review. Neurosci Biobehav Rev. 2019 Jul;102:139–52. doi: 10.1016/j.neubiorev.2019.04.010.
  8. Diatlova AS, Dudkov AV, Linkova NS, Khavinson VKh. Molekulyarnye markery kaspaza-zavisimogo i mitohondrial’nogo apoptoza: rol’ v razvitii patologii i v processah kletochnogo stareniya [Molecular markers of caspase-dependent and mitochondrial apoptosis: the role of pathology and cell senescence]. Advanc Modern Biol. 2018;138(2):126–37. Russian. doi: 10.7868/S0042132418020023.
  9. D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019 Jun;43(6):582–92. doi: 10.1002/cbin.11137.
  10. Jacotot É. Inhibition des caspases - De la biologie et thanatologie cellulaires au développement clinique de candidats médicaments [Caspase inhibition: From cellular biology and thanatology to potential clinical agents]. Med Sci (Paris). 2020 Dec;36(12):1143–54. French. doi: 10.1051/medsci/2020222.
  11. Muñoz-Pinedo C, López-Rivas A. A role for caspase-8 and TRAIL-R2/DR5 in ER-stress-induced apoptosis. Cell Death Differ. 2018 Jan;25(1):226. doi: 10.1038/cdd.2017.155.
  12. Kumar S. Caspase function in programmed cell death. Cell Death Differ. 2007 Jan;14(1):32–43. doi: 10.1038/sj.cdd.4402060.
  13. Levitan BN. Svyaz’ koncentracij antiendotoksinovyh antitel i faktora nekroza opuholej s patologiej gemostaza i fibrinoliza pri hronicheskih gepatitah i cirrozah pecheni [Relationship of antiendotoxin antibodies and tumor necrosis factor with pathology of hemostasis and fibrinolysis in chronic hepatitis and liver cirrhosis]. Thrombos Hemostas and Rheol. 2017;4:70–4. Russian. doi: 10.25555/THR.2017.4.0813.
  14. Topolyanskaya SV. Tumor Necrosis Factor-Alpha and Age-Related Pathologies. The Russian Archives of Internal Medicine. 2020;10(6):414–421. doi: 10.20514/2226-6704-2020-10-6-414-421.
  15. Voronina EV, Lobanova NV, Yakhin IR, Romanova NA, Seregin YuA. Role of tumor necrosis factor alpha in immune pathogenesis of different diseases and its significance for evolving anticytokine therapy with monoclonal antibodies. Medical Immunology (Russia). 2018;20(6):797–806. Russian. doi: 10.15789/1563-0625-2018-6-797-806.
  16. Xu X, Lai Y, Hua ZC. Apoptosis and apoptotic body: disease message and therapeutic target potentials. Biosci Rep. 2019 Jan 18;39(1):BSR20180992. doi: 10.1042/BSR20180992.
  17. Kuznik BI, Davydov SO, Landa IV. Faktor rosta nervov (NGF) i ego rol’ v usloviyah normy i patologii [Nerves growth factor (NGF) and its role in normal and pathology conditions]. Advan Physiolog Sci. 2019;50(4):64–80. Russian. doi: 10.1134/S0301179819040052.
  18. Santucci D, Racca A, Alleva E. When Nerve Growth Factor Met Behavior. Adv Exp Med Biol. 2021;1331:205–14. doi: 10.1007/978-3-030-74046-7_13.
  19. Kryzhanovskaya SYu, Zapara MA, Glazachev OS. Neurotrophins and adaptation to environmental stimuli: opportunities for expanding “therapeutic capacity” (mini-review). Herald of the International Academy of Science. Russian Section. 2020;1:36–43. Russian
  20. Levchuk LA, Vyalova NM, Mikhalitskaya EV, Semkina AA, Ivanova SA. The role of BDNF in the pathogenesis of neurological and mental disorders. Modern Probl Sci Educ. 2018;6. Available from: https://science-education.ru/ru/article/view?id=28267. Russian
  21. Ostrova IV, Golubeva NV, Kuzovlev AN, Golubev AM. Prognostic value and therapeutic potential of brain-derived neurotrophic factor (BDNF) in brain injuries (review). General Reanimatology. 2019;15(1):70–86. Russian. doi: 10.15360/1813-9779-2019-1-70-86.
  22. Brigadski T, Leßmann V. The physiology of regulated BDNF release. Cell Tissue Res. 2020 Oct;382(1):15–45. doi: 10.1007/s00441-020-03253-2.
  23. Cohen S, Gianaros PJ, Manuck SB. A Stage Model of Stress and Disease. Perspect Psychol Sci. 2016 Jul;11(4):456–63. doi: 10.1177/1745691616646305.
  24. Duman RS, Deyama S, Fogaça MV. Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants. Eur J Neurosci. 2021 Jan;53(1):126–39. doi: 10.1111/ejn.14630.
  25. Carr R, Frings S. Neuropeptides in sensory signal processing. Cell Tissue Res. 2019 Jan;375(1):217–25. doi: 10.1007/s00441-018-2946-3.
  26. Kanunnikova NP. Nejroprotektornye svojstva nejropeptidov [Neuroprotective properties of neuropeptides]. J Grodno State Med Univer. 2017; 15(5):492–8. Russian. doi: 10.25298/2221-8785-2017-15-5-492-498.
  27. Markelova EV, Zenina AA, Kadyrov RV. Neuropeptides as markers of brain damage. Modern Probl Sci Educ. 2018; 5. Available from: https://science-education.ru/ru/article/view?id=28099.
  28. Teplyashina EA, Olovyannikova RYa, Haritonova EV, Lopatina OL, Kutyakov VA, Pashchenko SI., Salmina AB. Nejropeptidy v regulyacii aktivnosti golovnogo mozga v norme i pri nejrodegeneracii [Neuropeptides in the regulation of brain activity in normal and neurodegeneration]. Probl Biol Med & Pharmac Chem. 2020;23(8):3–10. Russian. doi: 10.29296/25877313-2020-08-01.
  29. Nadorova AV, Kolik LG. Eksperimental’noe izuchenie vliyaniya peptidnogo anksiolitika selanka na kognitivnye funkcii, narushennye pri ostrom i hronicheskom dejstvii etanola [Experimental study of the effect of the peptide anxiolytic Selank on cognitive functions impaired by acute and chronic effects of ethanol]. Éksperimentalnaya i Klinicheskaya Farmakologiya. 2018;81(5s):168–168. Russian. DOI: 10.30906 / 0869-2092-2018-81-5s-168-168.
  30. Koroleva SV, Myasoedov NF. Semaks – universal’nyj preparat dlya terapii i issledovanij [Semax - a universal drug for therapy and research]. Bull Russ Acad Sci. Biolog Sec. 2018; 6: 669–82. Russian
  31. Tajti J, Szok D, Majláth Z, Tuka B, Csáti A, Vécsei L. Migraine and neuropeptides. Neuropeptides. 2015 Aug;52:19–30. doi: 10.1016/j.npep.2015.03.006.
  32. Verbenko VA, Shakina TA. Effectiveness of new synthesized analogue of endogenous peptide taftcin - Selank in therapy of adjustment and posttraumatic stress disorders. Medical alphabet. 2017;3(32):21–6. Russian
  33. Lyapina L.A., Grigor’eva M.E., Obergan T.Y., Maistrenko E.S. Rol’ peptidov tafcina i selanka v regulyacii pervichnogo i plazmennogo gemostaza [The role of the tuftsin and selank peptides in the regulation of primary and plasma homeostasis]. Izvestiia Akademii nauk. Seriia biologicheskaia. 2017;44(2):228–30. doi: 10.7868/S0002332917020126.
  34. Muronets E.M., Donskoy D.N., Pleten A.P. Nejropeptidy (obzor) [Neuropeptides (review)]. Concepts of Fundamental and Applied Scientific Research: Collect of Articles Intern Scientif and Practic Conf (May 20, 2018, Orenburg). Part 3.Ufa, 2018:135–9. Russian
  35. Vyunova TV, Andreeva LA, Shevchenko KV, Myasoedov NF. An integrated approach to study the molecular aspects of regulatory peptides biological mechanism. J Labelled Comp & Radiopharmaceutic. 2019;62(12):812–22. doi: 10.1002/jlcr.3785.
  36. Samotrueva MA, Yasenyavskaya AL, Murtalieva VK, Bashkina OA, Myasoedov NF, Andreeva LA, Karaulov AV. Experimental Substantiation of Application of Semax as a Modulator of Immune Reaction on the Model of “Social” Stress. Bull Exp Biol Med. 2019;Apr;166(6):754–8. doi: 10.1007/s10517-019-04434-y.
  37. Kudryavceva NN. Serotonergicheskij kontrol’ agressivnogo povedeniya: novye podhody – novye interpretacii (obzor) [Serotonergic Control of Aggressive Behavior: Novel Approaches--New Interpretations (Review)]. J High Nerv Activ. I.P. Pavlova. 2015;65(5):546–63. Russian. doi: 10.7868/S0044467715050081.
  38. Avgustinovich DF, Kovalenko IL, Kudryavtseva NN. A model of anxious depression: persistence of behavioral pathology. Neurosci Behav Physiol. 2005;Nov;35(9):917–24. doi: 10.1007/s11055-005-0146-6.
  39. Koolhaas JM, de Boer SF, Buwalda B, Meerlo P. Social stress models in rodents: Towards enhanced validity. Neurobiol Stress. 2016;Sep 23;6:104–12. doi: 10.1016/j.ynstr.2016.09.003.
  40. Bharani KL, Ledreux A, Gilmore A, Carroll SL, Granholm AC. Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer’s disease. Neurobiol Aging. 2020;Mar;87:49–59. doi: 10.1016/j.neurobiolaging.2019.11.010.
  41. Sun DB, Xu MJ, Chen QM, Hu HT. Significant elevation of serum caspase-3 levels in patients with intracerebral hemorrhage. Clin Chim Acta. 2017;Aug;471:62–7. doi: 10.1016/j.cca.2017.05.021.
  42. Chakrapani S, Eskander N, De Los Santos LA, Omisore BA, Mostafa JA. Neuroplasticity and the Biological Role of Brain Derived Neurotrophic Factor in the Pathophysiology and Management of Depression. Cureus. 2020;Nov 9;12(11):e11396. doi: 10.7759/cureus.11396.
  43. Colucci-D’Amato L, Speranza L, Volpicelli F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int J Mol Sci. 2020 Oct 21;21(20):7777. doi: 10.3390/ijms21207777.
  44. Lorente L, Martín MM, Pérez-Cejas A, González-Rivero AF, Argueso M, Ramos L, Solé-Violán J, Cáceres JJ, Jiménez A, García-Marín V. Serum caspase-3 levels during the first week of traumatic brain injury. Med Intensiva (Engl Ed). 2021;Apr;45(3):131–7. English, Spanish. doi: 10.1016/j.medin.2019.09.005.
  45. Ge N, Westbrook R, Langdon J, Yang H, Marx R, Abadir P, Xue QL, Walston JD. Plasma levels of corticosterone, tumor necrosis factor receptor 1 and interleukin 6 are influenced by age, sex and chronic inflammation in mice treated with acute temperature stress. Exp Gerontol. 2020;Dec;142:111136. doi: 10.1016/j.exger.2020.111136.
  46. YAsenyavskaya AL, Samotrueva MA, Myasoedov NF, Andreeva LA. Vliyanie semaksa na uroven’ interlejkina-1β v usloviyah “social’nogo” stressa [Influence of Semax on the level of interleukin-1βin the conditions of “social” stress]. Med Acad J. 19(1S):192–4. Russian. doi: 10.17816/MAJ191S1192-194.
  47. Yasenyavskaya AL, Samotrueva МА, Tsibizova АА, Myasoedov NF, Andreeva LA. Vliyanie gliprolinov na perekisnoe okislenie lipidov v gipotalamicheskoj i prefrontal’noj oblastyah golovnogo mozga v usloviyah “social’nogo” stressa [The influence of glyprolines on lipid peroxidation in the hypothalamic and prefrontal areas of the brain under conditions of “social” stress]. Astrakhan medical journal. 2020;15(3):79–85. Russian. doi: 10.17021/2020.15.3.79.85.
  48. Fricker LD. Carboxypeptidase E and the Identification of Novel Neuropeptides as Potential Therapeutic Targets. Adv Pharmacol. 2018;82:85–102. doi: 10.1016/bs.apha.2017.09.001.
  49. Thiele TE. Neuropeptides and Addiction: An Introduction. Int Rev Neurobiol. 2017;136:1–3. doi: 10.1016/bs.irn.2017.07.001.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Figure 1 – The nerve growth factor level in the blood serum of white rats under conditions of experimental “social” stress influenced by neuropeptides of the glyproline structure

Download (96KB)
Indexing metadata
3. Figure 2 – The brain neurotrophic factor level in the blood serum of white rats under conditions of experimental “social” stress influenced by neuropeptides of the glyproline structure

Download (93KB)
Indexing metadata

Copyright (c) 2021 Yasenyavskaya A.L., Tsibizova A.A., Andreeva L.A., Myasoedov N.F., Bashkina O.A., Samotrueva M.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies