| Autor: |
Bakaeva ZV; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia. bakaeva@nczd.ru., Surin AM; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia.; Institute of General Pathology and Pathophysiology, 125315, Moscow, Russia., Lizunova NV; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia.; Moscow State University, 119991, Moscow, Russia., Zgodova AE; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia.; The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation, 119146, Moscow, Russia., Krasilnikova IA; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia., Fisenko AP; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia., Frolov DA; MIREA-Russian Technological University, 119454, Moscow, Russia., Andreeva LA; Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia., Myasoedov NF; Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia., Pinelis VG; National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, 119296, Moscow, Russia. |
| Abstrakt: |
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 (ACTH 6-9 PGP), 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, ACTH 6-9 PGP and KKRRPGP protect neurons from the cells death, while PyrRP, conversely, enhances it. The neuroprotective effect of ACTH 6-9 PGP is accompanied by a slowdown in the development of delayed calcium dysregulation and synchronous mitochondrial depolarization. Among the studied peptides, only ACTH 6-9 PGP significantly increased the number of neurons that restored Ca 2+ homeostasis after Glu was abolished. The influence of KKRRPGP was less pronounced, whereas PyrRP, on the contrary, reduced the number of neurons with low [Ca 2+ ] i . Thus, this study revealed the high therapeutic significance of ACTH 6-9 PGP and allowed assessing the prospects for its possible clinical use. |
