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Neuroprotective Potential of Peptides HFRWPGP (ACTH6–9PGP), KKRRPGP, and PyrRP in Cultured Cortical Neurons at Glutamate Excitotoxicity

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
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Abstract

Glutamate (Glu) excitotoxicity, which accompanies brain ischemia or traumatic brain injury, is the leading mechanism of neuronal death. In the present work, we studied the effects of the peptides HFRWPGP (ACTH6–9PGP), KKRRPG, and PyrRP on the survival of cultured cortical neurons on the background of excitotoxic effect of Glu (100 µM). Biochemical (MTT/WST) and morphometric analyzes showed that, depending on the dose, ACTH6–9PGP and KKRRPGP protect neurons from the cells death, while PyrRP, conversely, enhances it. The neuroprotective effect of ACTH6–9PGP is accompanied by a slowdown in the development of delayed calcium dysregulation and synchronous mitochondrial depolarization. Among the studied peptides, only ACTH6–9PGP significantly increased the number of neurons that restored Ca2+ homeostasis after Glu was abolished. The influence of KKRRPGP was less pronounced, whereas PyrRP, on the contrary, reduced the number of neurons with low [Ca2+]i. Thus, this study revealed the high therapeutic significance of ACTH6–9PGP and allowed assessing the prospects for its possible clinical use.

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Funding

This work was supported by the Russian Foundation for Basic Research (project nos. 17-00-00105_COMFI and 17-00-00106_COMFI).

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Authors and Affiliations

  1. National Medical Research Center for Children’s Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia

    Z. V. Bakaeva, A. M. Surin, N. V. Lizunova, A. E. Zgodova, I. A. Krasilnikova, A. P. Fisenko & V. G. Pinelis

  2. Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia

    A. M. Surin

  3. Moscow State University, 119991, Moscow, Russia

    N. V. Lizunova

  4. The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation, 119146, Moscow, Russia

    A. E. Zgodova

  5. MIREA—Russian Technological University, 119454, Moscow, Russia

    D. A. Frolov

  6. Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia

    L. A. Andreeva &  N. F. Myasoedov

Authors
  1. Z. V. Bakaeva
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  2. A. M. Surin
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  3. N. V. Lizunova
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  4. A. E. Zgodova
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  5. I. A. Krasilnikova
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  6. A. P. Fisenko
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  7. D. A. Frolov
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  8. L. A. Andreeva
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  9. N. F. Myasoedov
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  10. V. G. Pinelis
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Corresponding author

Correspondence to Z. V. Bakaeva.

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

Statement on the welfare of animals. Animal experiments were performed in accordance with the regulations recommended by the European Science Foundation and the Order of the Ministry of Health of the Russian Federation “On Approval of the Rules of Good Laboratory Practice” no. 708n from August 23, 2010.

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Translated by M. Batrukova

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Bakaeva, Z.V., Surin, A.M., Lizunova, N.V. et al. Neuroprotective Potential of Peptides HFRWPGP (ACTH6–9PGP), KKRRPGP, and PyrRP in Cultured Cortical Neurons at Glutamate Excitotoxicity. Dokl Biochem Biophys 491, 62–66 (2020). https://doi.org/10.1134/S1607672920020040

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  • DOI: https://doi.org/10.1134/S1607672920020040

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