Assessment of antioxidant activity and cytotoxicity of the ±ktx-12 peptide in neuronal cell models

• Grant number: 23/04905-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2024
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Daniel Carvalho Pimenta
• Grantee: Lais Campelo Mendes
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Neurodegenerative diseases are characterized by progressive and irreversible loss of neuronal function. They share common features such as mitochondrial dysfunction, oxidative stress, and excitotoxicity. These aspects are primarily associated with the presence of reactive oxygen species resulting from oxidative stress, which leads to cellular damage. Treatment options for these diseases are severely limited. Consequently, there is growing interest in identifying new therapeutic targets, including the use of bioactive compounds such as neurotoxins that act on potassium channels.The objective of this study is to assess the antioxidant and cytotoxic activities of the ±-KTx12 peptide from the venom of Tityus bahiensis in different neuronal cell lines. Preliminary results in PC 12 cell cultures showed an increase in cell viability (as measured by crystal violet staining) over a 48-hour period at the lowest tested concentration of 0.005 µg/mL, while metabolic activity decreased. In the cytoprotection assay using the oxidizing agent H2O2, ±-KTX12 demonstrated reduced cell viability compared to all other groups at 12 hours. These findings suggest that modulation of the peptide on potassium channels positively affects cellular integrity and that its antioxidant activity reduces oxidative stress, contributing to cell preservation. Further steps involving label-free proteomic analysis in this experiment will provide additional insights into the peptide mechanism of action. (AU)