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.

• Tipo de documento: Artigo Científico
• Fonte: NEUROTOXICITY RESEARCH; v. 37, n. 1, p. 11-pg., 2019-10-25.

Resumo

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)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/24808-2 - Avaliação do potencial neuroprotetor de um peptídeo sintético em doenças neurodegenerativas: avaliação da genotoxicidade e mutagenicidade
• Beneficiário: Carolina Petri Bernardes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado