A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics

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

• Document type: Journal article
• Source: NEUROTOXICITY RESEARCH; v. 37, n. 1, p. 11-pg., 2019-10-25.

Abstract

The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells. Studies have demonstrated that acrolein might play an important role in the etiology of Alzheimer's disease (AD), which is characterized by neuronal and synaptic loss. Our results showed that not only acrolein reduced cell differentiation and cell viability, but also altered the expression of markers of synaptic communication (synapsin I), energy metabolism (AMPK-alpha, Sirt I and glucose uptake), and cytoskeleton (beta-III-tubulin). Treatment with p-BTX-I increased the percentage of differentiation in cells treated with acrolein and significantly attenuated cell viability loss, besides counteracting the negative effects of acrolein on synapsin I, AMPK-alpha, Sirt I, glucose uptake, and beta-III-tubulin. Additionally, p-BTX-I alone increased the expression of apolipoprotein E (apoE) gene, associated with the proteolytic degradation of beta-amyloid peptide aggregates, a hallmark of AD. Taken together, these findings demonstrate that p-BTX-I protects against acrolein-induced neurotoxicity and might be a tool for the development of novel drugs for the treatment of neurodegenerative diseases. (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
• FAPESP's process: 15/24808-2 - Neuroprotective potential evaluation of a synthetic peptide in neurodegenerative diseases: evaluation of genotoxicity and mutagenicity
• Grantee: Carolina Petri Bernardes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral