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

Author(s)

Bernardes, Carolina P. ; Santos, Neife A. G. ; Costa, Tassia R. ; Menaldo, Danilo L. ; Sisti, Flavia M. ; Amstalden, Martin K. ; Ribeiro, Diego L. ; Antunes, Lusania M. G. ; Sampaio, Suely V. ; Santos, Antonio C.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS; v. 29, n. 3, p. 16-pg., 2023-04-03.

Abstract

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, beta-III-Tubulin), and (ii) energy metabolism (AMPK-alpha 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. (AU)

• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support Opportunities: Research Projects - Thematic Grants