Effects of C-Terminal-Ethyl-Esterification in a Snake-Venom-Based Peptide Against the Neurotoxicity of Acrolein in PC12 Cells

• Published in: International journal of peptide research and therapeutics Vol. 29; no. 3; p. 41
• Main Authors: Bernardes, Carolina P., Santos, Neife A. G., Costa, Tassia R., Menaldo, Danilo L., Sisti, Flavia M., Amstalden, Martin K., Ribeiro, Diego L., Antunes, Lusânia M. G., Sampaio, Suely V., Santos, Antonio C.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 03-04-2023; Springer Nature B.V
• Subjects: Acetylation; Acrolein; Alzheimer's disease; Animal Anatomy; Animal models; Apolipoprotein E; Axonal plasticity; Axonogenesis; Biochemistry; Biomedical and Life Sciences; C-Terminus; Cognitive ability; Energy metabolism; Esterification; Histology; Kinases; Life Sciences; MAP kinase; Molecular Medicine; Morphology; N-Terminus; Neurodegenerative diseases; Neuroprotection; Neurotoxicity; Peptides; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pheochromocytoma cells; Polymer Sciences; Synapsin I; Synaptic plasticity; Tubulin; Venom; Neurotrophic effect; Acrolein; Neuroprotection; Snake-venom peptide; Terminal modification; Synaptic plasticity; Axonal plasticity
• ISSN: 1573-3904; 1573-3149; 1573-3904
• DOI: 10.1007/s10989-023-10517-2

We have recently reported the neurotrophic and neuroprotective effects of the snake-venom-based synthetic tripeptide BTX-I in PC12 cells treated with acrolein. In the present study, this peptide was chemically modified to increase its neurotrophic/neuroprotective activity. Esterification (ethyl or methyl), PEGylation and amidation were introduced at the C-terminus; acetylation was introduced at the N-terminus. The modified peptides protected PC12 cells from the decrease in viability and neuritogenesis induced by acrolein; however, only the ethyl-esterified peptide (named BTX-II) significantly increased neuritogenesis in comparison with the original peptide BTX-I. Moreover, BTX-II increased the expression of proteins related to (i) axonal/synaptic plasticity (synapsin I, β-III-Tubulin), and (ii) energy metabolism (AMPK-α and SIRT I) in PC12 cells treated with acrolein. In addition, BTX-II upregulated the expression of genes that encode apolipoprotein E (ApoE) and Mitogen-Activated Protein Kinase 3 (Mapk3), which are associated with cognitive improvements in animal models of Alzheimer’s disease (AD). In conclusion, ethyl-esterification at the C-terminus of the snake-venom-based tripeptide [Glu-Val-Trp] improved the neurotrophic and neuroprotective potential in relation to the original tripeptide.