ACTH(6–9)PGP Peptide Protects SH-SY5Y Cells from H₂O₂, <i>tert</i>-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Stimulation of Proliferation and Induction of Prosurvival-Related Genes

Abstract

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.

Keywords

• ACTH(6–9)
• neuroprotection
• MPP⁺
• H₂O₂
• <i>tert</i>-butyl hydroperoxide
• cyanide