ACTH(6–9)PGP Peptide Protects SH-SY5Y Cells from H<sub>2</sub>O<sub>2</sub>, <i>tert</i>-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Stimulation of Proliferation and Induction of Prosurvival-Related Genes
Mikhail G. Akimov,
Elena V. Fomina-Ageeva,
Polina V. Dudina,
Ludmila A. Andreeva,
Nikolay F. Myasoyedov,
Vladimir V. Bezuglov
Affiliations
Mikhail G. Akimov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Elena V. Fomina-Ageeva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Polina V. Dudina
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Ludmila A. Andreeva
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, Ploshchad’ Akademika Kurchatova 2, 123182 Moscow, Russia
Nikolay F. Myasoyedov
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, Ploshchad’ Akademika Kurchatova 2, 123182 Moscow, Russia
Vladimir V. Bezuglov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Stabilized melanocortin analog peptide ACTH(6–9)PGP (HFRWPGP) possesses a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we present a study of the proproliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6–9 (HFRW) linked with the peptide prolyine–glycyl–proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN and demonstrated proproliferative activity. The mechanism of its action was the modulation of proliferation-related NF-κB genes and stimulation of prosurvival NRF2-gene-related pathway, as well as a decrease in apoptosis.
