A tripeptide isolated from Bothrops atrox venom has neuroprotective and neurotrophic effects on a cellular model of Parkinson’s disease

•A tripeptide from Bothrops atrox venom was isolated and characterized.•It protects against apoptosis induced by MPP+ in PC12 cells.•It has neurotrophic effect on non-NGF-stimulated PC12 cells.•It protects against the impairment of differentiation in MPP+-treated PC12 cells.•It might be useful in th...

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Bibliographic Details
Published in:	Chemico-biological interactions 2015-06, Vol.235, p.10-16
Main Authors:	Martins, N.M., Santos, N.A.G., Sartim, M.A., Cintra, A.C.O., Sampaio, S.V., Santos, A.C.
Format:	Article
Language:	eng
Subjects:	1-Methyl-4-phenylpyridinium - pharmacology Animals Apoptosis - drug effects Bothrops - metabolism Bothrops atrox Caspase 3 - metabolism Caspase 9 - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Dopamine - metabolism Dopaminergic Neurons - drug effects Dopaminergic Neurons - metabolism Glutamic Acid - pharmacology Mitochondria - drug effects Mitochondria - metabolism Models, Biological MPP Neuroplasticity Neuroprotection Neuroprotective Agents - pharmacology Parkinson Disease - drug therapy Parkinson Disease - metabolism Parkinson’s disease PC12 Cells Peptides - pharmacology Rats Tryptophan - pharmacology Valine - pharmacology Venom peptide Venoms - pharmacology
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Summary:	•A tripeptide from Bothrops atrox venom was isolated and characterized.•It protects against apoptosis induced by MPP+ in PC12 cells.•It has neurotrophic effect on non-NGF-stimulated PC12 cells.•It protects against the impairment of differentiation in MPP+-treated PC12 cells.•It might be useful in the treatment of Parkinson’s disease. Parkinson’s disease (PD) is the second most common neurodegenerative disorder; however, there is no treatment able to prevent the loss of dopaminergic neurons or its consequences. Trophic factors such as NGF and BDNF has positive effects on different disorders of the brain, including neurodegeneration. Additionally, studies have suggested the use of venom peptides as a therapeutic strategy for neurological disorders. Therefore, in the present study, we investigated the neuroprotective activity of a peptide isolated from Bothrops atrox venom and its trophic ability by using a cellular model of dopaminergic neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells. We showed that it decreased the activities of the apoptotic proteases caspase-9 (mitochondrial) and caspase-3 (executor) and increased cell viability and proliferation in this model. Additionally, it increased neuritogenesis in non-treated PC12 cells (neuronal model) as well as in PC12 cells treated with the dopaminergic neurotoxin. The amino acid sequence of the peptide was identified as Glutamic acid–Valine–Tryptophan (Glu–Val–Trp). These findings suggest that this tripeptide has the potential to protect against the dopaminergic neurons loss and that trophic stimulation of neuroplasticity might be involved in its mechanism of neuroprotection.
ISSN:	0009-2797 1872-7786